Multiparametric MRI and Computational Modelling in the Assessment of Human Articular Cartilage Properties: A Comprehensive Approach

Abstract

Quantitative magnetic resonance imaging (qMRI) is a promising approach to detect early cartilage degeneration. However, there is no consensus on which cartilage component contributes to the tissue's qMRI signal properties. T1, T1ρ, and T2⁎ maps of cartilage samples (n = 8) were generated on a clinical 3.0-T MRI system. All samples underwent histological assessment to ensure structural integrity. For cross-referencing, a discretized numerical model capturing distinct compositional and structural tissue properties, that is, fluid fraction (FF), proteoglycan (PG) and collagen (CO) content and collagen fiber orientation (CFO), was implemented. In a pixel-wise and region-specific manner (central versus peripheral region), qMRI parameter values and modelled tissue parameters were correlated and quantified in terms of Spearman's correlation coefficient ρs. Significant correlations were found between modelled compositional parameters and T1 and T2⁎, in particular in the central region (T1: ρs ≥ 0.7 [FF, CFO], ρs ≤ −0.8 [CO, PG]; T2⁎: ρs ≥ 0.67 [FF, CFO], ρs ≤ −0.71 [CO, PG]). For T1ρ, correlations were considerably weaker and fewer (0.16 ≤ ρs ≤ −0.15). QMRI parameters are characterized in their biophysical properties and their sensitivity and specificity profiles in a basic scientific context. Although none of these is specific towards any particular cartilage constituent, T1 and T2⁎ reflect actual tissue compositional features more closely than T1ρ.

Human articular cartilage mechanosensitivity is related to histological degeneration – a functional MRI study

“…Moreover, condensation and deformation of the ECM induce interstitial water redistribution within and out of the tissue and increases in proteoglycan and collagen concentration 27 . As T1r is only weakly (if at all) associated with the individual tissue constituents 11,12,28 , it is the slow spinmotions and their interactions with the fluid and solid phases 29 that are the likely imaging correlates of the loading-induced increases in T1r. However, the exact sensitivity and specificity of T1r remains to be clarified with some studies suggesting specificity for proteoglycans 28,30 , while others refuted any such specificity 11,12 .…”

“…As T1r is only weakly (if at all) associated with the individual tissue constituents 11,12,28 , it is the slow spinmotions and their interactions with the fluid and solid phases 29 that are the likely imaging correlates of the loading-induced increases in T1r. However, the exact sensitivity and specificity of T1r remains to be clarified with some studies suggesting specificity for proteoglycans 28,30 , while others refuted any such specificity 11,12 . Nonetheless, it is commonly agreed that T1r is a surrogate parameter for the tissue's macromolecular constitution and functional properties 5,7,8,13,14 .…”

“…T1r is promising as it provides a quantitative measure of macromolecular content and biologically relevant changes. However, its exact structural and/or compositional determinants are still debated and specificity to distinct cartilage constituents is limited 11,12 . Furthermore, reports on loading-induced changes in T1r are inconsistent.…”

A serial multiparametric quantitative magnetic resonance imaging study to assess proteoglycan depletion of human articular cartilage and its effects on functionality

“…Under loading, the deeper radial collagen fibers display fiber crimping 31,39 , which increases the percentage of fibers oriented at magic angle and reduces residual dipolar interaction, thereby increasing T1ρ (as well as T2) values. Moreover, recent literature reports have disproven the previously assumed proteoglycan specificity of T1ρ and qualified this association as weak 35,40,41 so that loading-induced compositional changes may only be secondary. Consequently, T1ρ nowadays is considered a marker of the tissue's macromolecular constitution with sensitivity to its solid and fluid constituents.…”

“…Consequently, T1ρ nowadays is considered a marker of the tissue's macromolecular constitution with sensitivity to its solid and fluid constituents. Recently, positive correlations of T1ρ with fluid fraction and collagen fiber orientation, and negative correlations with collagen and proteoglycan content were reported 35 . Moreover, earlier studies by us and others have reported this parameter's exquisite mechanosensitivity and loading-induced changes in T1ρ in a range of pre-clinical and clinical contexts 17,21,22,42,43 .…”