T
2
and T
1
MRI in Articular Cartilage Systems
Nina M. Menezes,
1
Martha L. Gray,
1,2
James R. Hartke,
3
and Deborah Burstein
1,4
*
T
2
and T
1
have potential to nondestructively detect cartilage de-
generation. However, reports in the literature regarding their di-
agnostic interpretation are conflicting. In this study, T
2
and T
1
were measured at 8.5 T in several systems: 1) Molecular suspen-
sions of collagen and GAG (pure concentration effects): T
2
and T
1
demonstrated an exponential decrease with increasing [collagen]
and [GAG], with [collagen] dominating. T
2
varied from 90 to 35 ms
and T
1
from 125 to 55 ms in the range of 15–20% [collagen],
indicating that hydration may be a more important contributor to
these parameters than previously appreciated. 2) Macromole-
cules in an unoriented matrix (young bovine cartilage): In collagen
matrices (trypsinized cartilage) T
2
and T
1
values were consistent
with the expected [collagen], suggesting that the matrix per se
does not dominate relaxation effects. Collagen/GAG matrices (na-
tive cartilage) had 13% lower T
2
and 17% lower T
1
than collagen
matrices, consistent with their higher macromolecular concentra-
tion. Complex matrix degradation (interleukin-1 treatment)
showed lower T
2
and unchanged T
1
relative to native tissue,
consistent with competing effects of concentration and molecu-
lar-level changes. In addition, the heterogeneous GAG profile in
these samples was not reflected in T
2
or T
1
. 3) Macromolecules in
an oriented matrix (mature human tissue): An oriented collagen
matrix (GAG-depleted human cartilage) showed T
2
and T
1
varia-
tion with depth consistent with 16 –21% [collagen] and/or fibril
orientation (magic angle effects) seen on polarized light micros-
copy, suggesting that both hydration and structure comprise im-
portant factors. In other human cartilage regions, T
2
and T
1
ab-
normalities were observed unrelated to GAG or collagen orienta-
tion differences, demonstrating that hydration and/or molecular-
level changes are important. Overall, these studies illustrate that
T
2
and T
1
are sensitive to biologically meaningful changes in
cartilage. However, contrary to some previous reports, they are
not specific to any one inherent tissue parameter. Magn Reson
Med 51:503–509, 2004. © 2004 Wiley-Liss, Inc.
Key words: cartilage; MRI; Gd-DTPA
2-
; T
2
; T
1
Osteoarthritis (OA) is the most common form of arthritis,
currently affecting over 20 million people in the U.S.
alone. Among the earliest events in OA are molecular-level
changes in the two largest constituents of the cartilage
extracellular matrix, glycosaminoglycans (GAG) and col-
lagen (1). Specifically, GAG loss and collagen breakdown
herald the onset of OA (1,2). Thus, the early diagnosis of
OA requires the ability to noninvasively and nondestruc-
tively detect degenerative changes in GAG concentration
and collagen network integrity, a goal that has become
increasingly important as early-intervention therapies are
developed.
To this end, MRI has proven promising. Several MRI
parameters are actively being investigated for their ability
to reflect biochemical and structural information relevant
to the early stages of OA. However, the interpretation of
these parameters has not been fully elucidated. The main
goal of this work was to focus on two parameters in par-
ticular—T
2
and T
1
—and further investigate these MR pa-
rameters in model systems of cartilage.
T
2
has been studied extensively in cartilage. T
2
has
several sources of contributions. However, the current lit-
erature largely focuses on the source of T
2
contrast in
cartilage due to magic angle effects caused by the highly
organized collagen network of cartilage (3– 8). However,
Mosher et al. (9) have recently suggested that the magni-
tude of the magic angle effect in cartilage is small in in
vivo situations, and T
2
has also been investigated for its
dependence on hydration (collagen concentration) (10 –
13) and GAG concentration (14).
The literature regarding T
1
in cartilage provides con-
flicting results. One study found T
1
to be sensitive to
protein weight, concentration, and structure in suspen-
sions (15), suggesting that it may be sensitive to collagen in
cartilage. Studies of human cartilage from joint replace-
ment surgery found no correlation between T
1
and GAG
(14). Instead, T
1
was found to provide similar information
to T
2
. On the other hand, other studies demonstrated that
T
1
was shown to have high sensitivity to GAG in suspen-
sions (16,17) and GAG loss in bovine cartilage induced by
trypsin (16 –21), an enzyme that causes GAG loss but
spares intact collagen. Additionally, T
1
has been found to
be unchanged following treatment with collagenase (an
enzyme that cleaves collagen); together, these results lead
the authors to suggest that T
1
is selectively sensitive to
GAG (17,18).
In light of these conflicting results, the aim of this study
was to measure T
2
and T
1
in systems from the simplest to
most complex: suspensions of cartilage constituents (mo-
lecular suspensions without a matrix), bovine calf models
(structured macromolecular matrices that have no overall
orientation), to human tissue (oriented macromolecular
matrices). For the bovine and human samples we first
investigate collagen matrices (GAG-depleted tissue) and
then GAG/collagen matrices (normal tissue), and finally
complex degradation and disease models. dGEMRIC (de-
layed gadolinium-enhanced MRI of cartilage) and Tolu-
idine blue histology were used to assess GAG and polar-
ized light microscopy was used to assess collagen orienta-
tion for comparison to the T
2
and T
1
results.
1
Harvard–Massachusetts Institute of Technology Division of Health Sciences
& Technology, Cambridge, Massachusetts.
2
Department of Electrical Engineering & Computer Science, Massachusetts
Institute of Technology, Cambridge, Massachusetts, and New England Bap-
tist Bone and Joint Institute, Boston, Massachusetts.
3
Pharmacia Corp., St. Louis, Missouri.
4
Department of Radiology, Beth Israel Deaconess Medical Center, Boston,
Massachusetts.
Grant sponsor: National Institutes of Health; Grant numbers: AR42773;
RR14792; Grant sponsors: Edward Hood Taplin Professorship (to M.L.G.) and
the Natural Sciences and Engineering Research Council of Canada (to
N.M.M.).
*Correspondence to: Deborah Burstein, Ph.D., Beth Israel Deaconess Medi-
cal Center, Harvard Institutes of Medicine, room 148, 4 Blackfan Circle,
Boston, MA 02115. E-mail: dburstei@bidmc.harvard.edu
Received 19 February 2003; revised 8 October 2003; accepted 8 October
2003.
DOI 10.1002/mrm.10710
Published online in Wiley InterScience (www.interscience.wiley.com).
Magnetic Resonance in Medicine 51:503–509 (2004)
© 2004 Wiley-Liss, Inc. 503