Compositional MRI methods provide unique capabilities for imaging of changes in cartilage physiology, which are otherwise invisible using conventional morphological imaging methods. This presentation will provide an overview of methods for noninvasive imaging of cartilage such as T2 and T1ρ relaxation time mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glycosaminoglycan specific chemical exchange saturation transfer (gagCEST), diffusion tensor imaging (DTI), and sodium imaging. The presentation will discuss technical principles, validation studies, advantages, challenges and recent developments of each technique.
Compositional MRI techniques provide unique opportunity for imaging of subtle changes in cartilage physiology, which are not yet visible with conventional morphological imaging methods (1). Early changes in the extracellular matrix of cartilage are manifested by the loss of proteoglycans (PG) and the breakdown of the collagen network. Early detection of biochemical changes in cartilage therefore holds a potential for improved diagnostics, patient management and development of disease-modifying drugs.
This presentation will provide an overview of cartilage imaging techniques such as T2 and T1ρ relaxation time mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glycosaminoglycan (GAG) specific chemical exchange saturation transfer (gagCEST), diffusion tensor imaging (DTI), and sodium imaging. The technical principles, validation studies, advantages, challenges and recent developments will be discussed for each technique.
T2 mapping: T2 relaxation in cartilage is dominated by residual (static) dipolar interaction of water protons motionally restricted by the collagen network. T2 mapping therefore provides information on collagen and water content and on collagen orientation in cartilage. The orientational dependence of T2 results in laminal appearance of cartilage on T2 maps (2) and leads to an increase of T2 at the magic angle, when the orientation of collagen fibrils with respect to the B0 field is 54.7 degrees (3, 4). T2 values seem to be influenced also by PG content (5). In early stages of cartilage degeneration, loss of collagen and disorganization of matrix are reflected in elevated T2 values (6). The T2 mapping is usually performed with multi-echo spin echo sequence. Several steady-state sequences have been recently proposed for rapid T2 mapping such as 3D DESS (7), mcDESPOT (8) or 3D TESS (9). Bi-exponential fitting of T2 relaxation might be more sensitive to early degenerative changes (8, 10).
T1ρ mapping: First studies proposed that T1ρ relaxation in cartilage might be dominated by the chemical exchange and thus be sensitive to the PG concentration (11). However, recent publications suggest that the continuous-wave T1ρ mapping with spin-lock frequencies (SLF) equal or lower than 1000 Hz (limit on clinical MR systems) is substantially affected by the structure and orientation of the collagen matrix (12, 13). On the other hand, T1ρ mapping at higher SLF or using adiabatic T1ρ preparation shows lower orientational dependence (13, 14). The elevated T1ρ values were correlated with cartilage degeneration (15). T1ρ images acquired with different spin-locking times at a constant SLF are used for T1ρ mapping (16). Various approaches have been proposed to accelerate T1ρ mapping: MAPSS (17), balanced GRE (18), adiabatic T1ρ SWIFT (19), or combining compressed sensing with parallel imaging (20). T1ρ dispersion, i.e., T1ρ mapping at several different SLFs, allows to probe relaxation over a range of time scales which might provide new insights into cartilage composition.
dGEMRIC: dGEMRIC provides evaluation of the GAG concentration via the use of paramagnetic properties of a negatively charged gadolinium-based contrast agent (Gd(DTPA)2-), that accumulates in cartilage inversely with the GAG content (21). The degenerated tissue with lower GAG content therefore exhibits lower T1 values. The intravenous contrast administration is followed by exercise and delay allowing contrast diffusion prior to T1 mapping. The rate of the contrast accumulation may also be influenced by collagen content and orientation (22), pharmacokinetics (23) and exercise (24). Techniques such as inversion recovery (24) or more time-efficient 3D Look Locker method (25) and GRE with variable flip angles (26) were used for T1 mapping. Due to concerns about potential free gadolinium toxicity and restrictions on the use of Gd(DTPA)2- in European Union, macrocyclic gadolinium contrast agents are tested for dGEMRIC. Despite these drawbacks, dGEMRIC is one of the most easily applicable methods for the characterization of GAG content.
gagCEST: gagCEST
evaluates a decrease in water signal caused by the magnetization transfer of
selectively saturated protons of hydroxyl groups of GAGs to bulk water and thus
provides a measure of the GAG content (27, 28). Regions with a lower GAG concentration show
lower gagCEST values. gagCEST is a technically challenging technique that
requires sophisticated post-processing with motion- and B0-correction (29, 30). Due to a small resonance frequency difference
between water and hydroxyl protons, this technique remains very challenging at
3T (31). The gagCEST sequences typically use
frequency-selective continuous-wave saturation trains followed by a segmented
GRE readout (28-30). gagCEST does not require either exogenous
contrast agent or specialized hardware.
Diffusion tensor imaging: DTI applies diffusion-sensitizing gradients for measuring orientational dependence of water diffusion constrained by the cartilage extracellular matrix (32). While the mean diffusivity is sensitive to the PG content, fractional anisotropy provides information about collagen architecture (33). However, evaluation of the absolute PG or collagen concentration is not possible (34). DTI is technically challenging due to the short T2 in cartilage, low SNR, sensitivity to motion and the need for high spatial resolution (<1 mm). Different sequences such as LSDTI (35), diffusion-weighted 3D DESS (36) or diffusion prepared MAPSS (37) have been applied for in vivo diffusion measurements. Although DTI requires long acquisition times, it allows characterization of the most important cartilage macromolecules at the same time.
Sodium MRI: Sodium imaging measures positive sodium ions, which are in equilibrium with the fixed negative charge of GAGs and thus can be used for the evaluation of the PG content in cartilage (38). Due to a very short T2 and a relatively low sodium concentration, sodium MRI requires pulse sequences that allow using very short echo time (e.g. DA-RP (39), TPI (40) or vTE-GRE (41)) and a relatively long acquisition time (42). Due to low-resolution, sodium imaging is prone to partial volume artifacts. Various fluid suppression methods (43) or post-processing corrections based on measurement of cartilage thickness on morphological images (44) were proposed to account for this issue. Although sodium imaging requires specialized hardware and preferably a 7T MR system, it is sensitive to even small changes in the GAG concentration (45).
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