Erik Roessler1, Carlos Mattea1, Miika Nieminen2, Sakari Karhula2, Simo Saarakkala2, and Siegfried Stapf1
1Ilmenau University of Technology, Ilmenau, Germany, 2University of Oulu, Oulu, Finland
Synopsis
At low magnetic fields, T1
variation within cartilage is a robust parameter that is employed to quantify
the layered structure in the tissue and is sensitive to factors such as
enzymatic degradation, external load, and diseases such as osteoarthritis.
Variable-field relaxometry provides access to the content and local order of
glycosaminoglycans and collagen via proton-nitrogen quadrupolar dips. In this
study on 20 human cartilage samples, load-dependent low-field and
variable-field techniques were combined for the first time to correlate NMR
parameters with the severity of osteoarthritis.
INTRODUCTION
While T2 and T1ρ are becoming popular in clinical
studies of cartilage, their inherent dependence on sample orientation places a
limit to their diagnostic value. T1, on the other hand, is a robust
and isotropic parameter, and shows contrast rivalling or exceeding that of T2
when determined at fields below 0.5 T: the range of T1 at low fields
across cartilage is much more pronounced than any other tissue in the human
body. In addition, the amount of collagen and glycosaminoglycans can directly
be determined at fields close to 60 mT due to the signature of 14N
nuclei in the 1H relaxation dispersion curve. In this study, low-field
and variable-field NMR are combined for the first time with the purpose of quantifying
correlations with the degree of osteoarthritic degeneration in humans.METHODS
One-dimensional, depth-dependent
scans of bovine and human articular cartilage were carried out with spatial
resolutions between 20 and 50 μm on portable, single-sided scanners at magnetic field strengths of 0.27
T and 0.44 T, respectively. The spatial distributions of T2 and T1
were obtained with and without unidirectional compression at 0.6 MPa for the
human samples with different degrees of osteoarthritis, covering Mankin grades
0-12. The dispersion of T1 in the 1H Larmor frequency
range of 10 kHz to 30 MHz was monitored using a Stelar Fast Field Cycling relaxometer.RESULTS & DISCUSSION
The layered structure of mammalian
articular cartilage results in a pronounced T
2 variation at all
magnetic field strengths
1. A similar variation of T1,
typically covering a ratio of 3-5 between maximum and minimum values inside the
tissue, was identified at a field strength of 0.27 T, while it has been
reported as rather small at high magnetic field strengths
2. T
1
has thus been identified as a suitable parameter to follow changes in cartilage
properties by low-field NMR.
Average T
1, as well as
cartilage thickness obtained from T
1 measurements of human samples,
is found to correlate negatively with Mankin grade. At the same time, a significant
correlation was identified for relaxation time reduction before and after
uniaxial compression at 0.6 MPa, a typical value for forces appearing in the
human knee and hip joint. This finding is of importance since the spatial
resolution of 50 μm
obtained with the single-sided scanner is about one order of magnitude better
than the one in clinical high-field or low-field scanners
3, thus
allowing a much more reliable definition of thickness change which even
includes resolution of the three main cartilage layers.
At
1H Larmor frequencies
of 2-3 MHz, the
so-called quadrupolar dips are superimposed onto a frequency-dependent
signature of T
1 that can be approximated by power-laws. Varying the
composition, water content or structural integrity of cartilage affects both
the general frequency dependence of T
1 and the shape of the
quadrupolar dips, providing a possible diagnostic access to arthropathies such
as osteoarthritis (OA)
4. In this
study, a correlation of the area of the quadrupolar dips with Mankin grade is
demonstrated: diseased tissue contains less GAG but more water. The observation
is confirmed by artificially altered tissue using trypsin or collagenase
5,6.
CONCLUSIONS
Low-field MRI and variable-field
relaxometry were successfully combined in a study of osteoarthritic human
articular cartilage. Spin density and relaxation times were acquired normal to
the tissue plane with a spatial resolution of 50 μm or better; in particular, T1
showed a well-pronounced gradient across the tissue, unlike at clinical MRI
field strength. The degree of variation of these parameters was followed for
samples under load. Correlations of thickness change and T1 change
with disease state were observed. In variable-field experiments, the intensity
of quadrupolar dips and power-law parameters with disease state could be
demonstrated. These results allow for an improved diagnostic interpretation of
low-resolution clinical MRI particularly at dedicated extremity scanners.Acknowledgements
No acknowledgement found.References
[1]Xia Y, Magic-angle
effect in magnetic resonance imaging of articular cartilage – a review, Invest.
Radiol. 2000; 35: 602-621.
[2] Rössler E, Mattea C, Mollova A, Stapf S, Low-field
one-dimensional and direction-dependent relaxation imaging of bovine articular
cartilage, J. Magn. Reson. 2011; 213: 112-118.
[3] Rössler E, Mattea C, Stapf S, Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic
field using a single-sided NMR scanner applied to articular cartilage, J. Magn.
Reson. 2015; 251: 43-51.
[4] Broche LM, Ashcroft GP, Lurie DJ, Detection of
osteoarthritis in knee and hip joints by fast field-cycling NMR, Magn. Reson.
Med. 2012; 68: 358-362.
[5] Rössler E, Mattea C, Stapf S, NMRD investigations
of enzymatically degraded bovine articular cartilage, Magn. Reson. Med. 2015;
73:2005-2014.
[6] Rössler E, Mattea C, Saarakkala S, Lehenkari P, Finnilä
M, Rieppo L, Karhula S, Nieminen MT, Stapf S, Correlations of low-field NMR and
variable-field NMR parameters with osteoarthritis in human articular cartilage
under load, NMR in Biomedicine 2017; 30:
e3738/1-14.