Cartilage and Meniscus Assessment Using T1rho and T2 Measurements in Healthy Subjects and Patients with Osteoarthritis

Abstract

Objective

The purpose of this study was to evaluate meniscal degeneration in healthy subjects and subjects with osteoarthritis (OA) using T_1ρ and T₂ measurements and to examine the interrelationship between cartilage and meniscus abnormalities.

Methods

Quantitative assessment of cartilage and meniscus was performed using 3T MRI with a T_1ρ and T₂ mapping technique in 19 controls and 44 OA patients. A sagittal T₂-weighted fast spin echo (FSE) fat-saturated image was acquired for cartilage and meniscal Whole-Organ Magnetic Resonance Imaging Score (WORMS) assessment. Western Ontario and McMaster University (WOMAC) scores were obtained to assess clinical symptoms.

Results

The posterior horn of the medial meniscus (PHMED) had the highest incidence of degeneration. Stratifying subjects on the basis of PHMED grade revealed that the T_1ρ and the T₂ measurements of the PHMED and the medial tibial (MT) cartilage were higher in subjects having a meniscal tear (meniscal grade 2–4) compared to subjects with a mensical grade of 0 or 1 (p<0.05). While not statistically significant, there was a trend for T_1ρ and T₂ being higher in PHMED grade 1 compared to grade 0 (p=0.094, p=0.073 respectively). WOMAC scores had a stronger correlation with meniscus relaxation measures than cartilage measures.

Conclusions

MR T_1ρ and T₂ measurements provide a noninvasive means of detecting and quantifying the severity of meniscal degeneration. Meniscal damage has been implicated in OA progression and is correlated with cartilage degeneration. Early detection of meniscal damage represented by elevations in meniscal relaxation measures may identify subjects at increased risk for OA.

Introduction

Osteoarthritis (OA) is a heterogeneous disease characterized by the gradual loss of hyaline cartilage and is a whole-joint disorder involving the interaction between articular cartilage, subchondral bone, synovium, and the meniscus among others. The meniscus functions in joint stability, joint lubrication, shock absorption, and helps to maintain the integrity of the articular cartilage ^1–2. Previous studies have demonstrated that there is a high incidence of meniscal tears in patients with symptomatic arthritis as well as asymptomatic controls and that meniscal tears are associated with an increase in cartilage loss ^3–9.

Quantitative measurements of T_1ρ and T₂ relaxation times of cartilage provide a non-invasive means of detecting early biochemical changes in cartilage degeneration prior to morphological or clinical changes. A decline in the proteoglycan content, increase in the tissue water content, and alteration in the collagen content and orientation occur in cartilage during early osteoarthritis and can be quantified using T_1ρ and T₂ relaxation times ^10–11. In addition, cartilage T_1ρ and T₂ relaxation times are correlated with the severity of OA in vitro and in vivo ^12–16.

To our knowledge no study has investigated the relationship between T_1ρ and T₂ relaxation measures with the meniscal grades as assessed by a modified WORMS score ¹⁷. An increase in the intrameniscal signal or intrasubstance tear is commonly seen in asymptomatic subjects and represents an early stage in meniscus degeneration culminating in a meniscal tear most commonly seen in the posterior horn of the medial meniscus ^18–20. The purpose of our study was three-fold: 1) To evaluate T_1ρ and T₂ measurements of cartilage and meniscus with respect to morphological meniscal grade, 2) To examine the correlation of cartilage and meniscus T_1ρ and T₂ with clinical symptoms as assessed with the WOMAC score, and 3) To examine the interrelationship between measures of cartilage and meniscus degeneration.

Materials and methods

SUBJECTS

The patient recruitment for the study was a combination of referral by UCSF orthopaedic surgeons and recruitment from general public. The inclusion criteria for OA patients were frequent clinical symptoms of OA (including pain, stiffness and dysfunction) and demonstration of typical signs of OA in radiographs. The controls had no history of diagnosed OA, clinical OA symptoms, previous knee injuries, or signs of OA on radiographs.

Standard standing anteroposterior radiographs of the knee were obtained in all subjects at baseline to determine the Kellgren-Lawrence (KL) grade and OA severity ²¹. The 63 subjects (29 men, 34 women) that participated in this cross-sectional study had a mean age of 51±13.6 years and a mean BMI of 26.2±5.3 kg/m². Of these subjects, 19 were classified as controls (KL=0, mean age=39±10 yrs), 26 were classified as mild OA (KL score = 1 or 2, mean age=52±10 yrs), and 18 were classified as severe OA patients (KL score = 3 or 4, mean age=62±10 yrs). The subject characteristics are presented in Table 1.

Table 1.

Subject Characteristics stratified by KL grade.

						WOMAC
	Age (yrs)	Height (cm)	Weight (kg)	BMI	KL grade	Pain	Stiffness	Function
Controls (n=19)
Mean	39.10	172.5	70.79	23.47	0.00	3.26	1.63	6.79
SD	10.15	9.09	12.66	3.44	0.00	3.26	1.67	8.98
Mild OA (n=26)
Mean	52.27 *	170.04	75.28	26.00	1.46 *	3.19	1.88	10.42
SD	10.30	9.06	13.49	4.01	0.51	3.14	1.24	11.11
p-value (vs. controls)	<0.001			0.200		0.998	0.842	0.551
Severe OA (n=18)
Mean	62.61* #	166.58	80.89	29.33* #	3.47 *#	10.72* #	4.67 *#	35.55 *#
SD	10.33	8.48	16.67	6.78	0.52	4.48	1.64	14.15
p-value (vs. controls)	<0.001			0.001		<0.001	<0.001	<0.001
p-value (vs. mild OA)	0.005			0.071		<0.001	<0.001	<0.001
ANOVA Prob >F	<0.001	0.137	0.106	0.002		<0.001	<0.001	<0.001
Patients (mild and severe)
Mean	56.50 *	168.62	77.57	27.36 *		6.27 *	3.03 *	20.70 *
SD	11.42	8.89	14.95	5.50		5.26	1.97	17.53
p-value (vs. controls)	<0.001	0.120	0.089	0.006		0.025	0.009	0.002

^*Significantly different than control (p<0.05).

^#Significantly different than mild OA (p<0.05)

BMI=body mass index; KL= Kellgren-Lawrence; WOMAC=Western Ontario and McMasters Universities Arthritis Index; SD= standard deviation. Controls are defined as subjects having a KL score of 0, Mild OA are defined as subjects with a KL score of 1 or 2, and Severe OA are defined as subjects having a KL score of 3 or 4.

All of the subjects included in the study were in good health as assessed by a medical history and physical examination and had no contraindications to MR imaging. All subjects completed the Western Ontario and McMasters University (WOMAC) questionnaire to assess pain, stiffness, and function of the knee joint through a 5-point scale ²². The study was approved by the local Institutional Review Board and conducted in accordance with the Committee for Human Research. All subjects gave written informed consent prior to participation in the study.

MAGNETIC RESONANCE IMAGING PROTOCOL

MRI of the knee was performed using a 3T GE Excite Sigma MR Scanner (General Electric, Milwaukee, WI, USA) and an 8-channel phased-array knee coil (Invivo, Orlando, FL, USA). In the OA subjects, the knee with more severe findings on the radiographs was imaged. In control subjects, the dominant leg was imaged. Parallel imaging was performed with an array spatial sensitivity technique (ASSET) using acceleration factor (AF) = 2. Cartilage volume and thickness were assessed using a high spatial resolution volumetric fat-suppressed spoiled-gradient-echo (SPGR) sequence (repetition time TR/TE= 15/6.7 ms, flip angle=12, field of view (FOV) =14 cm, matrix=512 × 512, in-plane spatial resolution=0.273 × 0.273 mm², slice thickness= 1mm, BW=31.25 kHz, number of excitations=0.75, acquisition time= 7 m 37 s). A T₂-weighted fat-saturated FSE sequence (TR/TE = 4300/51ms, FOV = 14 cm, matrix = 512 × 256, slice thickness (ST) = 2.5 mm, gap = 0.5 mm) was used to determine the clinical WORMS measurements for the cartilage and the meniscus.

Sagittal three-dimensional T_1ρ and T₂ sequences were used to assess the cartilage and meniscus sub compartments. The T_1ρ was obtained using a spin-lock technique followed by SPGR acquisition using transient signals evolving towards steady-state with the following parameters: TR/TE= 9.3/3.7 ms, time of recovery = 1500ms, FOV= 14 cm, matrix= 256 × 192, slice thickness= 3 mm, BW= 31.25 kHz, views per segment= 48, time of spin-lock (TSL)= 0/10/40/80 ms, FSL= 500 Hz, acquisition time of approximately 13 min ²³. The T₂ quantification was also based on a magnetization preparation sequence with 3D SPGR using transient signals evolving towards steady-state ²⁴. The T₂ preparation pulses contained an MLEV train of nonselective composite 90_x180_y90_x refocusing pulses. The imaging parameters were the same as the T_1ρ quantification except for magnetization preparation TE = 3.1/13.5/23.9/44.8 ms. The T₂ quantification sequence covered the same region as T_1ρ quantification, and had an acquisition time of 11 min.

MR IMAGING ANALYSIS

Morphological Analysis

The clinical assessment of cartilage, meniscus, and ligaments was performed using a sagittal T₂-weighted FSE fat-saturated image by two experienced radiologists (TML with 20 and JBP with 9 years of experience). The radiologists were blinded to subject information and relaxation data, and performed separate readings, with a consensus in the case of disagreement.

Meniscal scoring was graded using a modified WORMS score of the knee as follows: 0= no lesion, 1= intrasubstance abnormality, 2= non-displaced tear, 3=displaced or complex tear without deformity, and 4=maceration of the meniscus ¹⁷. Meniscal scores 2 through 4 were collapsed into one category to represent the group with a meniscal tear. The meniscal WORMS sum was calculated as a sum of the meniscal WORMS scores for every compartment.

Ligaments were graded using a modified WORMS score of the knee as follows: 0=no lesion, 1= signal abnormality around the ligament, 2=signal abnormality within the ligament, 3=partial tear, 4=complete tear ¹⁷. The ligaments that were graded included the following: anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL).

Quantitative Assessment

All MR images were transferred to a Sun Workstation (Sun Microsystems, Palo Alto, CA) for data processing and quantification of cartilage volume, cartilage thickness, and T_1ρ and T₂ relaxation measurements of cartilage and meniscus. Cartilage sub compartments were segmented semi-automatically in high resolution SPGR images using the in-house software developed with Matlab (Mathworks, Natick, MA, USA) based on edge detection and Bezier splines. Cartilage segmentation was performed by investigators with extensive experience in performing cartilage segmentation. The cartilage compartments analyzed included the following: lateral femoral condyle (LFC), medial femoral condyle (MFC), lateral tibia (LT), medial tibia (MT), and the patella (P). Cartilage thickness and volume measurements were determined using the in-house software developed with Matlab. Previous studies have shown that variations in joint size have a greater effect on cartilage volume than cartilage thickness ²⁵. Therefore, cartilage volume was normalized by dividing the cartilage volume by the epicondylar distance to account for differences in joint size amongst subjects.

The meniscus compartments were segmented using a T_1ρ image with TSL = 40 ms, rigidly registered to the SPGR image using the VTK CISG Registration Toolkit. The meniscus compartments analyzed included the following: anterior horn lateral meniscus (AHLAT), anterior horn medial meniscus (AHMED), posterior horn lateral meniscus (PHLAT), and posterior horn medial meniscus (PHMED). The meniscal body was excluded because of partial volume effects. The anatomical landmarks defined for meniscus segmentation have been previously described in detail ²⁶. Additional studies from our laboratory utilizing the same techniques and protocols for cartilage and meniscus quantification have reported good reproducibility and precision ^26–27. Specifically, the CVs for the reproducibility for the T_1ρ are: 4.6% for the AHLAT, 3.3% for the PHLAT, 3.7% for the AHMED, and 4.9% for the PHMED ²⁷. The CVs for the T₂ are: 8.91% for the AHLAT, 10.57% for the PHLAT, 7.44% for the AHMED, and 9.35% for the PHMED ²⁶.

T_1ρ and T₂ maps were reconstructed by fitting the T_1ρ and T₂ images pixel by pixel using a Levenberg-Marquardt mono-exponential fitting algorithm developed in-house using the equations below:

$$\begin{array}{c}S(\mathit{\text{TSL}})\propto \text{exp}(-\mathit{\text{TSL}}/T_{1\rho })\text{for}\mathrm{T}1\text{rho}\hfill \\ S(\mathit{\text{TE}})\propto \text{exp}(-\mathit{\text{TE}}/T_2)\text{for}\mathrm{T}2\hfill \end{array}$$

For cartilage, all four T_1ρ or T₂-weighted images were used to reconstruct the maps. For meniscus, only the first three T_1ρ or T₂-weighted images were used. T_1ρ-weighted images with TSL=80 ms and T₂-weighted images with TE=44.8 ms had a very low SNR (<5) for meniscus due to short T_1ρ and T₂ in meniscus respectively, and therefore were not used during map reconstruction. The reconstructed T_1ρ and T₂ maps were then rigidly registered to the SPGR image using VTK CISG Registration Toolkit ²⁸. 3D cartilage and meniscus contours after segmentation were overlaid to T_1ρ and T₂ maps. Mean T_1ρ and T₂ values were calculated in defined regions. T_1ρ and T₂ measurements were then compared between subjects with a meniscal grade of 0, 1, and those with a meniscal tear (grades 2–4) (Figure 1).

Figure 1. T1rho and T2 in the posterior horn of the medial meniscus.

MR images showing the posterior horn of the medial meniscus in a control subject with a posterior horn medial meniscus WORMS grade of 0 (A, B, C), a mild OA subject with a posterior horn medial meniscus WORMS grade of 1 (D, E, F), and a mild OA subject with a posterior horn medial meniscus WORMS grade of 3 (G, H, I). The differences in the FSE images (A, D, G), T1rho (B, E, H), and T2 (C, F, I) can been seen clearly between the subjects with different meniscal grades. The color bar indicates the gradation of relaxation measures.

STATISTICAL ANALYSIS

All statistical analyses were conducted using JMP software, version 8.0 (SAS Institute, Cary NC). All of the analyses were conducted using 2-tailed tests and a p-value of less than 0.05 was considered statistically significant. Analysis of variance (ANOVA) was used to assess the differences between the subject characteristics and relaxation measurements by KL grade and meniscal grade. Post-hoc comparisons were made with Tukey Honestly Significant Difference Test (HSD), using an α of 0.05. In cases where the ANOVA test was statistically significant, the p-values for the post-hoc analysis are reported. We did not make statistical adjustments for weight or BMI because there was no statistical difference in weight or BMI between the PHMED grades (p=0.198 for weight, p=0.099 for BMI). Spearman correlation coefficient measurements were conducted to assess the correlations of relaxation measurements of cartilage and meniscus compartments with WOMAC scores as well as the correlations of meniscal WORMS sum with WOMAC scores.

Results

SUBJECT CHARACTERISTICS

The number of subjects having a mensical tear in a location other than the PHMED was very low. Therefore, because we did not have the statistical power to analyze the other meniscal compartments, we focused our analysis on the PHMED.

Table 2 shows the subject characteristics stratified by three groups of PHMED grade based on meniscal WORMS assessment: meniscal grade 0 (n=23), meniscal grade 1 (n=17), and meniscal grades 2–4 (n=23). Subjects with meniscal grades 2–4 had statistically higher WOMAC scores compared to subjects with a meniscal grade 0 (p=0.005, p=0.005, and p=<0.001 for pain, stiffness, and function respectively). WOMAC scores for meniscal grade 1 were not statistically different than grade 0 (p=0.511, 0.252, and 0.169 for pain, stiffness, and function respectively) or grade 2–4 (p=0.148, 0.347, 0.220 for pain, stiffness, and function respectively). There were no statistically significant differences in height, weight, or BMI between subjects stratified by meniscal grade (p= 0.210, p=0.198, p=0.099 for height, weight, and BMI respectively).

Table 2.

Subject characteristics stratified by posterior horn medial meniscal grade.

						WOMAC
	Age (yrs)	Height (cm)	Weight (kg)	BMI	Pain	Stiffness	Function
Meniscus Grade 0 (n=23)
Mean	42.9	171	72.5	24.4	3.30	1.69	7.88
SD	10.5	7.23	10.7	3.46	3.08	1.49	9.68
Mensicus Grade 1 (n= 17)
Mean	51.4 *	167	73.7	26.5	4.94	2.65	16.76
SD	11.9	10.8	16.5	5.94	4.94	1.73	17.0
p-value (vs. grade 0)	0.070				0.511	0.252	0.169
Meniscus grades 2–4 (n= 23)
Mean	59.5 *	170	79.8	27.7	7.74 *	3.48 *	25.0 *
SD	12.8	9.07	15.8	5.87	5.53	2.23	18.1
p-value (vs. grade 0)	<0.001				0.005	0.005	< 0.001
p-value (vs. grade 1)	0.090				0.148	0.347	0.220
ANOVA Prob > F	<0.001	0.210	0.198	0.099	0.007	0.008	0.001

^*Significantly different than meniscal grade 0 (p<0.05).

^#Significantly different than meniscal grade 1 (p<0.05).

BMI= body mass index; SD= standard deviation.

MENISCAL ASSESSMENT

Table 3 illustrates the incidence of meniscal grade by KL group and by meniscal sub compartment. The overall incidence of meniscal tears was 16% in controls and 57% in OA patients. Among OA patients, 42% of mild OA and 78% of severe OA patients had a meniscal tear. The incidence of a meniscal tear was the highest in the posterior horn of the medial meniscus regardless of KL group.

Table 3.

Meniscal Grade by collapsed meniscal grading scheme.

	Grade 0	Grade 1	Grades 2–4 collapsed
LATERAL MENISCUS
Anterior horn
Control (n=19)	19 (100%)	0 (0%)	0 (0%)
Mild OA (n=26)	19 (73.97%)	3 (11.54%)	4 (15.38%)
Severe OA (n=18)	10 (55.55%)	3 (16.67%)	5 (27.78%)
All subjects, %(n=63)	76.19	9.52	14.29
Posterior horn
Control (n=19)	19 (100%)	0 (0%)	0 (0%)
Mild OA (n=26)	19 (73.08%)	1 (3.85%)	6 (23.08%)
Severe OA (n=18)	10 (55.56%)	4 (22.22%)	4 (22.22%)
All subjects, % (n=63)	76.19	7.94	15.87
MEDIAL MENISCUS
Anterior horn
Control (n=19)	18 (94.74%)	0 (0%)	1 (5.26%)
Mild OA (n=26)	25 (96.15%)	1 (3.85%)	0 (0%)
Severe OA (n=18)	12 (66.67%)	3 (16.67%)	3 (16.67%)
All subjects, % (n=63)	87.30	6.35	6.35
Posterior horn
Control (n=19)	12 (63.16%)	5 (26.31%)	2 (10.53%)
Mild OA (n=26)	9 (34.61%)	9 (34.61%)	8 (30.77%)
Severe OA (n=18)	2 (11.11%)	3 (16.67%)	13 (72.22%)
All subjects, % (n=63)	36.51	26.98	36.51

Meniscal grade by collapsed meniscal grading scheme. The table illustrates the distribution of subjects by meniscal grading schemes and KL grade. Each column shows the number of subjects assigned to the meniscal grade. The percentage in parenthesis represents the percentage of subjects in each KL grade that have a given meniscal grade. Controls are defined as subjects having a KL score of 0, Mild OA are defined as subjects with a KL score of 1 or 2, and Severe OA are defined as subjects having a KL score of 3 or 4.

LIGAMENT ASSESSMENT

Control subjects had no ligament abnormalities. Among OA subjects, 20% had a signal abnormality around (WORMS=1) or within (WORMS=2) a ligament (13.6% ACL, 6.82% PCL), 2.27% had a partial ACL degenerative tear (WORMS=3), and 4.55% had a complete degenerative ACL tear (WORMS=4).

CARTILAGE MORPHOMETRY MEASUREMENTS

Figures 4 shows the cartilage thickness and normalized volume measurements respectively of the medial femoro-tibial cartilage compartment in subjects stratified by PHMED grade. The only cartilage compartment that was statistically different between the meniscal grades was the MT. The MT cartilage thickness was 17% lower and the normalized volume was 24% lower in the meniscal grade 2–4 group compared with grade 0 (p=0.027, p=0.024 respectively).

T1rho AND T2 RELAXATION MEASUREMENTS STRATIFIED BY PHMED GRADE

Stratifying the data by PHMED grade produced similar trends for T_1ρ and T₂ relaxation. Figures 5 and 6 show the T_1ρ and T₂ relaxation times respectively, in subjects stratified by PHMED grade for cartilage and the meniscus. The MT was the only cartilage compartment that was statistically different between meniscal grades, the T_1ρ and T₂ of meniscal grade 2–4 being higher than grade 0 (p=0.017 for T_1ρ, p=0.001 for T₂) and grade 1 (p=0.027 for T_1ρ, p<0.001 for T₂). However, MT cartilage T_1ρ and T₂ relaxation times were not statistically different between meniscal grade 0 and 1 (p=0.998 for T_1ρ, p=0.873 for T₂).

With respect to meniscal compartments, the meniscal grade 2–4 group had higher T_1ρ and T₂ relaxation times in the PHLAT (p=0.043 for T_1ρ, p=0.035 for T₂) and the PHMED (p<0.001 for T_1ρ and T₂) compared to grade 0. The PHMED was the only compartment that had statistically different T_1ρ and T₂ times between more than one meniscal grade. Specifically, the T_1ρ and the T₂ values in the PHMED grade 2–4 were higher than grade 0 (p<0.001 for T_1ρ and T₂) and grade 1 (p<0.001 for T_1ρ and T₂). Furthermore, there was a trend for T_1ρ and T₂ being higher in PHMED grade 1 compared to grade 0 (p=0.094 for T_1ρ, p=0.073 for T₂).

CORELATION BETWEEN T1rho and T2 with WOMAC SCORES

Correlations of cartilage and meniscus T_1ρ and T₂ relaxation with clinical WOMAC scores are shown in Table 7. WOMAC scores were more strongly correlated with the meniscus than cartilage, with 3 of 4 meniscal compartments, having significant correlations with the total WOMAC scores compared with only 2 of the 5 cartilage compartments. The PHMED had the strongest correlation with WOMAC scores. While both T_1ρ and T₂ meniscal measurements in the PHMED, AHLAT, and the PHLAT, demonstrated significant correlations with WOMAC scores, T₂ consistently had a higher correlation than the T_1ρ. The medial cartilage compartment (MFC and MT) demonstrated significant correlations between T_1ρ and WOMAC pain, stiffness, and total score. This same relationship applied with regard to cartilage T₂ and WOMAC scores in MT, but not in MFC.

Table 7.

Correlations of T1rho and T2 relaxation times [ms] with WOMAC Scores.

	Pain		Stiffness		Function		Total
	T1ρ	T2	T1ρ	T2	T1ρ	T2	T1ρ	T2
CARTILAGE
LFC	0.123	0.130	0.249*	0.089	0.231	0.135	0.216	0.134
p-value	0.338	0.308	0.049	0.486	0.068	0.289	0.089	0.293
MFC	0.302*	0.227	0.371*	0.234	0.298*	0.127	0.314*	0.161
p-value	0.016	0.074	0.003	0.065	0.018	0.322	0.012	0.206
LT	−0.028	0.149	0.148	0.252*	0.031	0.212	0.028	0.208
p-value	0.825	0.245	0.242	0.047	0.807	0.096	0.817	0.102
MT	0.331*	0.387*	0.304*	0.371*	0.270*	0.415*	0.294*	0.417*
p-value	0.008	0.002	0.015	0.003	0.033	<0.001	0.019	<0.001
Patella	0.021	0.227	0.108	0.164	0.098	0.153	0.085	0.174
p-value	0.868	0.079	0.403	0.205	0.449	0.239	0.512	0.180
MENISCUS
AHMED	−0.341	0.259*	0.011	0.142	−0.022	0.174	−0.018	0.186
p-value	0.793	0.042	0.905	0.269	0.864	0.176	0.891	0.148
PHMED	0.503*	0.526*	0.403*	0.404*	0.502*	0.550*	0.501*	0.533*
p-value	<0.001	<0.001	0.001	0.001	<0.001	<0.001	<0.001	<0.001
AHLAT	0.319*	0.3956*	0.296*	0.352*	0.256	0.208*	0.268*	0.305*
p-value	0.014	0.002	0.023	0.007	0.050	0.048	0.040	0.020
PHLAT	0.419	0.414*	0.361*	0.325*	0.419*	0.351*	0.422*	0.364*
p-value	<0.001	<0.001	0.004	0.010	<0.001	0.005	<0.001	0.004

^*Correlation coefficient significant at p<0.05.

WOMAC=Western Ontario and McMasters Universities Arthritis Index; LFC=lateral femoral condyle; MFC=medial femoral condyle; LT=lateral tibia; MT=medial tibia; AHMED=anterior horn medial meniscus; PHMED=posterior horn medial meniscus; AHLAT=anterior horn lateral meniscus; PHLAT=posterior horn lateral meniscus.

Correlations of meniscal WORMS sum with WOMAC scores were as follows: 0.437 for pain, 0.483 for stiffness, and 0.578 for function (p<0.001 for all measures). These correlations were similar to the correlations of PHMED T2 with WOMAC scores.

Discussion

In this cross-sectional study quantitative MRI was used to evaluate T_1ρ and T₂ relaxation measurements in subjects with various grades of meniscal degeneration. Our results indicate that quantitative MRI measurements of T_1ρ and T₂ can not only distinguish between subjects with a normal meniscus and those with a meniscal tear, but it can also distinguish between subjects with increased intra-substance signal and those with a meniscal tear. Correlation data reveal that clinical WOMAC scores are more closely related to T_1ρ and T₂ of the meniscus than T_1ρ and T₂ of cartilage.

Clinical Findings

Our finding of a 16% incidence of mensical tears in controls and 57% incidence in the OA patients is similar to previous reports but differs from other studies involving an older subject population (65 vs. 51 yrs) ^{3–4, 7}. Because the incidence of meniscal tears increases with age, the difference in age between the study participants may account for the discrepancy ^{20, 29}.

Consistent with the findings of others we report a higher prevalence of meniscal abnormalities in the posterior horn of the medial meniscus regardless of KL grade (Table 3) ^{20, 29–31}. The medial meniscus has a decreased mobility, larger diameter, and smaller thickness relative to other meniscal locations and thus may have an increased susceptibility of damage ²⁰. Furthermore, the highest weight-bearing pressure is in the medial compartment. In the normal state 60–80% of the total intrinsic compressive load is transmitted across the knee in the medial compartment ³².

In addition to the increased meniscal damage in the medial compartment, like others, we also report a significantly decreased cartilage thickness and volume in the MT in subjects with a PHMED tear (Table 4) ^5–6,31. These findings are all consistent with previous reports demonstrating that the medial compartment is the site of the most structural changes during the early course of osteoarthritis ³³.

Table 4.

Cartilage morphology measures stratified by posterior horn medial meniscus grade.

	CARTILAGE THICKNESS (mm)				CARTILAGE VOLUME (mm3)
	LFC	MFC	LT	MT	LFC	MFC	LT	MT
Meniscus Grade 0 (n=23)	1.50	1.48	1.95	1.35	503	365	253	182
Mean	0.264	0.334	0.351	0.276	145	136	88.7	53
SD
Mensicus Grade 1 (n= 17)
Mean	1.53	1.49	1.74	1.29	449	353	216	159
SD	0.317	0.279	0.533	0.280	152	118	92.7	56
p-value (vs. grade 0)				0.797				0.426
Meniscus Grades 2– 4 (n= 23)
Mean	1.59	1.30	1.70	1.12*	488	289	205	138*
SD	0.355	0.376	0.470	0.291	195	128	91.9	54
p-value (vs. grade 0)				0.027				0.024
p-value (vs. grade 1)				0.174				0.477
ANOVA Prob > F	0.608	0.106	0.148	0.029	0.620	0.123	0.191	0.031

^*Significantly different than meniscal grade 0 (p<0.05).

^#Significantly different than meniscal grade 1 (p<0.05).

LFC=lateral femoral condyle; MFC=medial femoral conydle; LT=lateral tibia; MT=medial tibia; SD= standard deviation.

Consistent with previous reports, we report that the ACL was the ligament with the highest incidence of abnormality ³⁴. However, since only 4.55% of patients had a complete ACL degenerative tear the focus of this investigation was on meniscal abnormalities.

T1rho and T2 measurements of cartilage and meniscus

Both cartilage and meniscus consist of a macromolecular framework of collagen fibers, proteoglycan, and water, albeit in different concentrations. Articular cartilage is primarily composed of type II collagen and 5–10% proteoglycan, while the meniscus is composed of 98% type I collagen and only 1% proteoglycan ^{27, 35}. In hyaline cartilage, T_1ρ relaxation is inversely related to proteoglycan content while T₂ relaxation is related to cartilage collagen orientation and water content ^{10, 36–38}. The mechanisms of T_1ρ and T₂ relaxation in the meniscus are not fully understood, and therefore our understanding of the biochemical mechanism of T_1ρ and T₂ is based upon on the findings in hyaline cartilage.

Subjects with a PHMED tear had higher T_1ρ and T₂ in the PHMED compared to subjects without meniscal damage. Histological studies indicate that articular cartilage and meniscal degeneration results in alterations in the matrix including the deterioration and disorientation of the collagen network, decline in the proteoglycan content, an increase in water content, and an infiltration of synovial fluid into the damaged location ^30,39.The decline in proteoglycan content decreases the resiliency of the cartilage and meniscus while the disorganization of the collagen network compromises the ability of the tissues to withstand the compressive forces. A mensical tear may also contribute to altering the biomechanical properties of the articular cartilage and meniscus, altering joint stability, and impairing balance ^40–41. Together these biochemical and biomechanical alterations may account for the elevations in T_1ρ and T₂ seen in the MT cartilage and the posterior meniscus in the presence of a PHMED tear.

Our findings indicate that T_1ρ and T₂ measurements can distinguish between some of the different meniscal grades. Specifically, T_1ρ and T₂ of the PHMED could not only distinguish between subjects with and without a meniscal tear but could also distinguish between subjects with an intrasubstance meniscal degeneration and those with a meniscal tear. The magnitude of T_1ρ and T₂ was directly related to the severity of the meniscal degeneration. While not statistically significant, there was a trend showing higher T_1ρ and T₂ in subjects with an intrasubstance meniscal degeneration compared to subjects with a normal meniscus.

The results of this study have important implications for early detection and intervention. The intrasubstance meniscal abnormality represents an early degenerative change in the meniscus that predisposes individuals to further damage or progression to a meniscal tear ^{19, 39, 42}. Furthermore, meniscal tears are significantly associated with an increased progression of OA ^5–9. Therefore, being able to distinguish between meniscal grades using T_1ρ and T₂ provides a noninvasive means of detecting and monitoring the degenerative changes in the meniscus. Furthermore, because relaxation times provide a continuous variable of tissue properties, they may be used to objectively diagnose early meniscal degeneration prior to a diagnosis based on categorical meniscal grading.

Quantitative MRI offers an advantage over arthroscopy in regards to meniscal assessment ^19,43. While arthroscopy can only examine the surface areas of the meniscus, MR imaging can examine the entire meniscus ³⁰. Furthermore, the PHMED is difficult to visualize using arthroscopy, accounting for the decreased accuracy of detection of meniscal tears ^{19, 30,43}. In contrast, MRI can be used to accurately detect meniscal tears in the medial compartment. Lastly, while arthroscopy can only detect the presence of a meniscal tear, quantitative MR imaging provides the unique ability to detect the presence of early meniscal degeneration ¹⁹. Early detection may allow clinicians to intervene early to minimize the need for arthroscopic surgery. Previous studies demonstrate that nonoperative treatment of patients with meniscal degeneration is effective in improving function ⁴⁴.

Interrelationship Between Cartilage and Meniscus

The elevation in the T_1ρ and T₂ seen in the MT cartilage in subjects with a PHMED tear is consistent with our finding of a corresponding decrease in cartilage thickness in this region (Table 4). Previous studies investigating the effect of meniscal tears on cartilage loss have reported similar results ³¹. The MT cartilage may have the greatest cartilage loss because it lies adjacent to the area of meniscal damage and withstands the greatest weight-bearing load ⁴⁵. Our finding of cartilage damage and loss occurring in a compartment adjacent to a damaged meniscal compartment underscores the interrelationship between cartilage and the meniscus.

Correlation of T1rho and T2 the clinical WOMAC scores

To our knowledge this is the first study to investigate the correlation between clinical WOMAC scores and T_1ρ and T₂ in cartilage and meniscus subcompartments. Looking at a similar subject population as ours, Rauscher et al. reported that the T_1ρ and T₂ measurements of the medial, lateral, and both menisci were correlated wit h WOMAC scores ²⁶. However, meniscal sub compartments and cartilage measurement correlations were not reported. Our findings indicate that WOMAC scores were more strongly correlated with the meniscus than cartilage, and there was a direct relationship between the strength of the correlation and the incidence of meniscal tears. These findings may be explained by the fact that articular cartilage is avascular and aneural while the outer one-third of the meniscus is vascularized, contains nerves, and nociceptive fibers ^46–47.

Comparing the correlation results of the T_1ρ data to the T₂ data, we found that cartilage T_1ρ had a stronger correlation with WOMAC scores, while meniscal T₂ had a stronger correlation with WOMAC scores (Table 7). The finding that T_1ρ is a more sensitive indicator of clinical cartilage parameters than T₂ is consistent with previous reports showing that T_1ρ is a more sensitive indicator of cartilage degeneration than T₂ ¹⁶. One of the factors that may account for this finding is that T_1ρ has a more dynamic range and is more sensitive at detecting changes in chondral defects than T₂ ⁴⁸. Furthermore, the higher proteoglycan concentration in articular cartilage may explain the stronger relation between T_1ρ and cartilage, while the higher collagen concentration and low proteoglycan content in the meniscus may account for the stronger relationship between T₂ and the meniscus. Together these findings indicate that T_1ρ may be more suitable at measuring the dynamic changes in articular cartilage, while T₂ may be more appropriate for measuring the dynamic changes in the meniscus associated with OA progression.

WOMAC correlations revealed that the WOMAC pain scores had a stronger correlation with the T_1ρ and the T₂ of the PHMED than the meniscal WORMS sum. These results indicate that relaxation measures of the PHMED may provide a more accurate assessment of pain measures than morphological meniscal parameters.

Limitations

One of the limitations is that we were unable to measure meniscal extrusion and joint alignment because we did not acquire coronal images or long limb radiographs. Both of these factors are associated with cartilage loss and OA progression and therefore this may be a confounding factor ^{6, 32,49}. Another limitation is the relatively small sample size and the cross-sectional design. The results of the current study are exploratory and longitudinal studies using a larger cohort are needed to confirm these findings.

In conclusion, we have shown that quantitative MRI measures of T_1ρ and T₂ offer a noninvasive means of early detection of cartilage and meniscus degeneration. Most importantly, because relaxation measures provide a continuous variable of tissue properties, this information may be used to accurately and objectively diagnose early meniscal degeneration prior to a diagnosis made using a categorical grading system.

Table 5.

Cartilage and Meniscus T1rho stratified by posterior horn medial meniscal grade.

	CARTILAGE T1rho (ms)				MENISCUS T1rho (ms)
	LFC	MFC	LT	MT	AHLAT	PHLAT	AHMED	PHMED
Meniscus Grade 0 (n=23)
Mean	39.87	41.48	35.36	34.86	13.47	12.50	12.42	13.94
SD	4.18	5.39	4.08	4.20	2.79	2.26	2.11	2.00
Mensicus Grade 1 (n= 17)
Mean	40.48	42.14	36.07	34.78	14.14	14.36	13.13	17.16
SD	3.86	3.85	4.10	3.45	3.56	4.54	2.65	3.72
p-value (vs. grade 0)				0.998	0.862	0.176		0.094
Meniscus grades 2– 4(n= 23)
Mean	41.99	44.15	37.37	39.34*#	16.44*	14.87*	13.73	23.73*#
SD	4.10	4.63	5.84	7.23	4.85	2.85	3.09	6.96
p-value (vs. grade 0)				0.017	0.036	0.043		<0.001
p-value (vs. grade 1)				0.027	0.187	0.878		<0.001
ANOVA Prob > F	0.204	0.151	0.365	0.008	0.037	0.042	0.256	<0.001

^*Significantly different than meniscal grade 0 (p<0.05).

^#Significantly different than meniscal grade 1 (p<0.05).

LFC=lateral femoral condyle; MFC=medial femoral condyle; LT=lateral tibia; MT=medial tibia; AHLAT=anterior horn lateral meniscus; PHLAT=posterior horn lateral meniscus; AHMED=anterior horn medial meniscus; PHMED=posterior horn medial meniscus; SD= standard deviation.

Table 6.

Cartilage and Meniscus T2 stratified by posterior horn medial meniscal grade.

	CARTILAGE T2 (ms)				MENISCUS T2 (ms)
	LFC	MFC	LT	MT	AHLAT	PHLAT	AHMED	PHMED
Meniscus Grade 0 (n=23)
Mean	32.63	32.14	27.73	28.14	10.78	10.42	11.18	11.26
SD	2.94	3.35	4.53	4.03	2.40	1.45	1.88	1.51
Mensicus Grade 1 (n= 17)
Mean	33.24	33.34	27.87	27.41	11.96	12.06*	11.81	13.51
SD	2.61	2.43	4.99	2.72	3.40	2.77	1.69	2.53
p-value (vs. grade 0)				0.873		0.048		0.073
Meniscus grades 2– 4 (n=23)
Mean	33.14	32.98	30.06	33.08*#	12.85	12.03*	12.36	17.89*#
SD	2.76	6.04	4.81	5.82	3.91	2.12	2.09	4.51
p-value (vs. grade 0)				0.001		0.035		<0.001
p-value (vs. grade 1)				<0.001		1.00		<0.001
ANOVA Prob > F	0.751	0.667	0.197	<0.001	0.122	0.019	0.125	<0.001

^*Significantly different than meniscal grade 0 (p<0.05).

^#Significantly different than meniscal grade 1 (p<0.05).

LFC=lateral femoral condyle; MFC=medial femoral condyle; LT=lateral tibia; MT=medial tibia; AHLAT=anterior horn lateral meniscus; PHLAT=posterior horn lateral meniscus; AHMED=anterior horn medial meniscus; PHMED=posterior horn medial meniscus; SD= standard deviation.