European Journal of Radiology 83 (2014) 984–988
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
T2 mapping in patellar chondromalacia Fernando Ruiz Santiago a,∗ , Rocío Pozuelo Calvo b , Julio Almansa López c , Luis Guzmán Álvarez a , María del Mar Castellano García a a b c
Department of Radiology, Traumatology Hospital, University Hospital Virgen de las Nieves, Granada, SPAIN Department of Rehabilitation and Physical therapy, Traumatology Hospital, University Hospital Virgen de las Nieves, Granada, SPAIN Department of Physic, University Hospital Virgen de las Nieves, Granada, SPAIN
a r t i c l e
i n f o
Article history: Received 26 September 2013 Received in revised form 16 February 2014 Accepted 7 March 2014 Keywords: Chondromalacia patellae Cartilage Magnetic resonance imaging T2 relaxation time T2 mapping
a b s t r a c t Objective: To study the correlation between the T2 relaxation times of the patellar cartilage and morphological MRI findings of chondromalacia. Methods: This prospective study comprises 50 patients, 27 men and 23 women suffering of anterior knee pain (mean age: 29.7, SD 8.3 years; range: 16–45 years). MRI of 97 knees were performed in these patients at 1.5 T magnet including sagittal T1, coronal intermediate, axial intermediate fat sat and T2 mapping. Chondromalacia was assessed using a modified version of Noyes classification. The relaxation time, T2, was studied segmenting the full thickness of the patellar cartilage in 12 areas: 4 proximal (external facet–proximal–lateral (EPL), external facet–proximal–central (EPC), internal facet–proximal–central (IPC), internal facet–proximal–medial (IPM), 4 in the middle section (external facet–middle–lateral (EML), external facet–middle–central (EMC), internal facet–middle–central (IMC), internal facet–middle–medial (IMM) and 4 distal (external facet–distal–lateral (EDL), external facet–distal–central (EDC), internal facet–distal–central (IDC), internal facet–distal–medial (IDM). Results: T2 values showed a significant increase in mild chondromalacia regarding normal cartilage in most of the cartilage areas (p < 0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM. Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistical significant differences in comparison with normal cartilage, except in EMC and IMC, where similar values as mild chondromalacia were maintained (p < 0.05). Conclusions: Steepest increase in T2 values of patellar cartilage occurs in early stages of patellar cartilage degeneration. Progression of morphologic changes of chondromalacia to more severe degrees is associated to a new drop of T2 relaxation times approaching basal values in most of the areas of the patellar cartilage, except in the central area of the middle section, where T2 values remain increased. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Chondromalacia is a pathological condition of articular cartilage. In early stages of chondromalacia cartilage is softened, swollen or fibrillated; fragmentation, fissuring and subchondral bone abnormalities are present in advanced stages. Clinical findings are not reliable indicators for its diagnosis because many cases are asymptomatic. Morphological MRI, one of the preferred methods for studying articular cartilage lesions, is highly sensitive for detecting severe cartilage lesions, but its sensitivity is low for mild or incipient injury [1]. Physiologic MRI includes sequences that examine cartilage composition and increase sensitivity for early
∗ Corresponding author. Tel.: +34 627633829. E-mail address: [email protected] (F. Ruiz Santiago). http://dx.doi.org/10.1016/j.ejrad.2014.03.007 0720-048X/© 2014 Elsevier Ireland Ltd. All rights reserved.
cartilage degeneration. Early detection of cartilage injury is important because it may explain patients’ symptoms and influence short and long-term outcomes [2,3]. Quantitative T2 mapping has been reported as a technique to study the compositional integrity of cartilage. Increased cartilage T2 relaxation times have been associated with matrix damage, specifically with the loss of collagen integrity and the increase of water content. However, the role of T2 mapping at different stages of cartilage degeneration is not well defined [4]. Studies performing laminar analysis of cartilage in the knee have shown that the outer layers (articular surface layers) have higher T2 values than the basal bone surface layers. As the cartilage degenerates, the outer layer is eventually lost (falls off), therefore bringing mean values back down [5]. In this paper we try to correlate the T2 relaxation times of the patellar cartilage with morphological MRI findings of chondromalacia. Relating T2 values of cartilage to current staging of
F. Ruiz Santiago et al. / European Journal of Radiology 83 (2014) 984–988
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chondromalacia would strengthen the clinical usefulness of T2 mapping, increasing the role of MRI monitoring cartilage lesions and therapy effects [6]. 2. Methods 2.1. Subjects and study design This prospective study comprises 50 patients, 27 men and 23 women recruited during 2011 (mean age: 29.7, SD 8.3 years; range: 16–45 years). They presented uni or bilateral anterior Knee pain. All patients provided informed consent to participate in the study, which was approved by the institutional review board. Inclusion criteria were: age between 15 and 45 years and patellofemoral pain during at least 3 months, on either knee. Exclusion criteria were: history of previous knee surgery and the presence of clinical signs or imaging findings of articular narrowing, osteophytes, tendonitis, and meniscal or ligament injury. Pain was assessed using a visual analogue scale (VAS). Time of evolution and pain characteristics were registered, including the influence of activities that flex the knee, such as walking, running, prolonged sitting, squatting and ascending or descending stairs. Physical exam was performed in the rehabilitation department at the recruitment site. The physical exam included observation of static alignment of the lower extremity, evaluation of the range of motion, palpation of patellar and adjacent patellar structures, strength evaluation and special tests, such as patellar tilt, patellar compression, eccentric step and patellar apprehension tests [7]. According to physical and radiological findings knees were classified as asymptomatic, pain associated to instability or idiopathic patellofemoral pain. 2.2. Imaging studies All patients underwent MRI of both knees, even asymptomatic knees, except three of them in whom only the symptomatic knee was studied. That accounts for the 97 knees included in this study. MRI was performed at 1.5 T machine (HDx; GE Healthcare Systems, Wisconsin) using a quadrature transmit-receive coil. This included sagittal T1 (TR: 500 ms; TE: 9.5 ms); coronal intermediate (TR: 1.880 ms; TE: 44.6 ms) and axial intermediate fat sat (TR: 2.200 ms; TE: 41.4 ms) weighted images. The last sequence, T2 mapping, consisted in a multi-slice multi-echo fast spin echo (FSE) pulse sequence acquired across the length of the patella. Eight echo images were acquired at each slice location (TR: 1.000 ms; TE: 7.8, 15.7, 23.6, 31.4, 39.3, 47.2, 55.1 and 62.9 ms; FOV: 14; matrix: 256 × 160; thickness: 3 mm; gap: 0.6 mm). 9 slices per patella were procured (Fig. 1).
Fig. 1. An ROI was placed in12 locations: external–proximal–lateral external–proximal–central (EPC), internal–proximal–central (EPL), internal–proximal–medial (IPM), external–middle–lateral (IPC), external–middle–central (EMC), internal–middle–central (EML), internal–middle–medial (IMC), (IMM), external–distal–lateral (EDL), external–distal–central (EDC), internal–distal–central (IDC), internal–distal–medial (IDM). Global ANOVA values for each location are shown.
The relaxation time, T2, was studied segmenting the patellar cartilage in 12 areas (Fig. 1): 4 proximal (external facet–proximal–lateral (EPL), external facet–proximal–central (EPC), internal facet–proximal–central (IPC), internal facet–proximal–medial (IPM)), 4 in middle section (external facet–middle–lateral (EML), external facet–middle–central (EMC), internal facet–middle–central (IMC), internal facet–middle–medial (IMM)) and 4 distal (external facet–distal–lateral (EDL), external facet–distal–central (EDC), internal facet–distal–central (IDC), internal facet–distal–medial (IDM)). The central line was traced between the central crest of the bone separating both facets and the central crest of the cartilage covering the bone. Therefore, the segmented areas were symmetrical in Wiberg type I patella and asymmetrical in types II and III, where external areas are greater than internal areas, according to the size of its respective facets. The global T2 value was calculated by manually placing a region of interest (ROI) that covered the full thickness of patellar cartilage in each location. It was accomplished by simultaneously examining the T2 map and the anatomic sequence (in neighboring image panels) with synchronized cursor, slice number and zoom. First at all, the middle line slice was chosen and then, the central slice of the proximal and distal half of the patellar cartilage was selected and segmentation at the three slices performed as shown in Fig. 1. T2 relaxation time was calculated by fitting an exponential function to the signal intensity at different echo times as follows: SI (TE) ∼ exp (–TE/T2), where SI (TE) is signal intensity as a function of echo
2.3. Image analysis For the sake of consistency, chondral injuries were assessed by an experimented musculoskeletal radiologist (20 years) using a modified version of the Noyes classification system of articular cartilage defects of the knee joint [8]: grade 0, intact cartilage with normal signal and uniform thickness; grade I, focal abnormal signal without surface abnormalities; grade II, superficial ulceration or fissuring, with a depth of no more than 50% of cartilage thickness; grade III, deep ulceration or fissuring of more than 50% but less than a 100% of cartilage thickness; grade IV, full-thickness cartilage defect with edema or erosion of subchondral bone. If different grades of cartilage lesions were present, the worst lesion was used for grading the severity of affectation of patellar cartilage (Fig. 2). For statistical analysis, chondromalacia grades I and II were regrouped as mild and grades III and IV as severe.
Fig. 2. Chondromalacia grade I (A), II (B), III (C) and IV (D) of Noyes modified.
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Table 1 Association between clinical diagnosis and the presence of chondromalacia. No statistical differences were found (P = 0.051). Clinical diagnosis Cartilage
Asymptomatic
Instability
Idiopatic pain
Total
Normal Mild chondromalacia Severe chondromalacia Total
20 3 5 28
10 10 6 26
20 9 14 43
50 22 25 97
time, TE is echo time, and T2 is the transverse relaxation time [9]. T2 is defined as the time at which the signal decays to 37% of maximum signal [10]. 2.4. Statistical analysis To avoid interobserver errors, a musculoskeletal radiologist made all measurements unaware of final clinical diagnosis. To estimate intraobserver error, we randomly chose 16 knees to be measured by the same examiner on successive days. This measurement error was calculated by the coefficient of intraclass correlation [11]. For statistical analysis each knee was considered as independent. Comparison of T2 relaxation times in different quadrants between knees with different grades of chondromalacia and without chondromalacia was performed by repeated measures analysis of variance (ANOVA) [12]. Bonferroni test was performed when statistical significance was achieved in ANOVA tests. Statistical software SPSS version 15 was used. Power is the probability that if a difference exists, we find it. It was determined based on one way ANOVA analysis and calculated using a type I error of 0.05, considering the mean T2 values in each area according to the degree of chondromalacia, the percentage of knees in each group and the conjoined standard deviation of groups. Ene 3.0 software was used. 3. Results
Fig. 3. Graphic depicting the evolution of T2 relaxation values with different stage of patellar cartilage chondromalacia. EPL: external–proximal–lateral; IPC: internal–proximal–central; IPM: internal–proximal–medial; external–middle–lateral; EMC: external–middle–central; IMC: EML: internal–middle–central; EDC: external–distal–central.
3.4. Relationship between changes in cartilage T2 and severity of patellar chondromalacia Comparison of T2 relaxation values in each patellar cartilage quadrant of patients without chondromalacia versus patients with mild and severe chondromalacia was performed. Global Anova results are indicated in Fig. 1. Bonferroni post hoc multiple comparison results are depicted in Table 2 and Fig. 3. T2 values showed a significant increase in mild chondromalacia with regard normal cartilage in all quadrants (p < 0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM (mean: 2.3 ± 0.3 ms; median: 2.35 ms; range: 0.9 ms (IDM)–4.0 ms (IPM)). Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistically significant differences with regard to normal cartilage, except in EMC and IMC, where it maintained similar values as mild chondromalacia (p < 0.05).
3.1. Patients’ clinical features
4. Discussion
Of 97 analysed Knees, 28 were asymptomatic, 26 diagnosed as pain secondary to instability and 43 as idiopathic patellofemoral pain. Mean value of VAS score in symptomatic knees was 4.3 ± 0.3 and mean length of pain was 49.5 ± 5.7 months. No statistical differences were found when these parameters were compared between different clinical diagnoses.
The transverse relaxation time constant, T2, of articular cartilage has been proposed as a biomarker for cartilage integrity. There is good evidence that T2 mapping is useful for identifying sites of early-stage degeneration (early disruption of the collagen matrix) in cartilage, which appears as areas with T2 higher than that of normal cartilage [13]. This is due to increased permeability of the matrix, which leads to increased content and motion of water. Some studies show elevated T2 not only in areas of cartilage damage but also in adjacent areas, suggesting exposure of additional hydrophilic sites close to the injured cartilage areas leading to fluid accumulation and a lengthening of T2 relaxation time [14]. There has not been established any linear relationship between T2 values and osteoarthritis grades that could aid in the differentiation between mild and more severe disease. In a previous study, it was demonstrated that increase of T2 relaxation times of tibial and femoral cartilage correlate with severity of osteoarthritis (OA), but similar T2 values for subjects with moderate and severe OA were found [13]. It was hypothesised that water motility is increased in degenerated cartilage, lengthening relaxation times. Nevertheless, although our work agrees with this by demonstrating no further increase of T2 values with progression of the chondromalacia, a T2 relaxation time shortening tendency has been observed as a novel datum in severe chondromalacia, approaching that of normal cartilage in some areas. This shows that increased water content
3.2. Prevalence of chondromalacia and relationship with clinical diagnosis With regard to the presence of cartilage lesions, 50 knees were considered normal (grade 0), while chondromalacia of the patella was diagnosed in 47 knees, 22 as mild (7 grade I, 15 grade II) and 25 as severe (5 grade III, 20 grade IV) chondromalacia. Association between clinical diagnosis and the presence of chondromalacia is shown in Table 1. 3.3. Measurement error The intraclass correlation of intraobserver measurements ranged from the lower value at the IMM localization (0.632, moderate agreement) to the greater value at IDC localization (0.953, excellent agreement).
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Table 2 T2 relaxation values of areas of patellar cartilage with significant results after Bonferroni test. Power of the test in each area is shown. Values are expressed as mean ± standard error of the mean. N: normal cartilage; MC: mild chondromalacia; SC: severe chondromalacia; EPL: external–proximal–lateral; IPC: internal–proximal–central; IPM: internal–proximal–medial; EML: external–middle–lateral; EMC: external–middle–central; IMC: internal–middle–central; EDC: external–distal–central. Location
Normal
MC
SC
Significance
Power
EPL IPC IPM EML EMC IMC EDC
41.0 ± 0.5 41.8 ± 0.4 44.1 ± 0.7 37.4 ± 0.4 38.6 ± 0.4 39.7 ± 0.4 40.9 ± 0.6
43.4 ± 0.6 44.5 ± 0.7 48.1 ± 1.1 40.0 ± 1.0 40.9 ± 1.0 42.0 ± 1.2 44.0 ± 0.7
42.0 ± 0.6 42.3 ± 0.7 45.3 ± 0.7 39.5 ± 0.9 41.5 ± 1.0 42.8 ± 0.8 42.7 ± 1.0
P = 0.039: N versus MC P = 0.009: N versus MC P = 0.005: N versus MC P = 0.039: N versus MC P = 0.018: N versus SC P = 0.013: N versus SC P = 0.025: N versus MC
57.84 74.16 78.64 69.15 75.19 77.45 67.29
and mobility might only be a manifestation of early degenerative changes, while progression of cartilage injury is accompanied by a lost capacity to retain water by the damaged cartilage, which is redistributed to other locations. This would be in agreement with previous works that found elevation of the mean T2 values and increased heterogeneity of cartilage T2 relaxation time as indicative of early cartilage biochemical degeneration [5,15,16]. Apprich et al. found a significant increase of T2 relaxation times in femoral condyle cartilage with the presence of cartilage defect grade ≤2 using the International Cartilage Repair Society (ICSR) classification system; this is similar to that we have classified as mild chondromalacia [17]. Nevertheless, Koff et al. did no found any increase in T2 values in patellar cartilage in patients with different grades of osteoarthritis, determined in plain radiographs by the Kellgren (KL) method [18]. These last authors stated that the KL staging would detect accurately advanced stages of OA rather than the onset of the disease. Therefore, if there is a rapid change of T2 values during the onset of OA and not at later stages, differences of T2 values using a KL protocol for staging OA cannot be expected. That may fit with our results, where severe degrees of chondromalacia, even without radiographic signs of OA, are characterized by a drop or maintenance of T2 values with regard of those present in early mild cartilage degeneration. Although in the previous Stehling’s paper [9] it is stated that a significant correlation between patellar cartilage T2 values and the severity and grade of cartilage does exist, this conclusion was obtained trough a multiple linear regression analysis and the correlation coefficient value was not specified. That only indicates a linear relationship between the presence of chondromalacia and the increase of T2 values. The authors did not compare T2 values between groups of different severities of chondromalacia, but patients with and without chondromalacia. This study agrees with our findings, since we also observed that when we grouped our cohort’s mild and severe chondromalacia patients together, T2 values were higher than those of patients with normal cartilage. Chondromalacia within various areas of the patellar cartilage can be governed by different mechanisms. It is widely recognized that articular surfaces are not affected equally by chondromalacia and that certain areas are particularly prone to damage [19]. Fulkerson stated that chondromalacia along the lateral facet of the patella often relates to chronic patellar tilt and excessive lateral pressure syndrome, whereas chondromalacia of the medial facet is commonly related to patellar dislocation [20]. This trend has not been demonstrated in our work, with medial and lateral facets of the patella affected, independent of the clinical diagnosis. Nevertheless, we found that changes in T2 times are more strongly accentuated in central areas of the patellar cartilage. This finding may be in agreement with the arthroscopy review of Hunt et al. [19] that found that distal medial cartilage of the patella is less affected in idiopathic chondromalacia and lateral patellar maltracking. Therefore, in clinical practice, T2 values must be interpreted in combination with morphological findings. Strong rising of T2 values is associated with early chondromalacia according to Noyes’
classification; while advanced stage cartilage degeneration shows quite similar T2 values than normal cartilage in most of the cartilage surface, but can easily be diagnosed by morphological findings. The main limitation of our study is the lack of surgical confirmation of chondromalacia. Although arthroscopy is nowadays considered the gold standard for diagnosis of cartilage injury, detection of low-grade lesions with this orthopaedic technique is also difficult and the validity of this evaluation depends on the surgeon’s experience [21]. Another theoretical limitation is placement of the ROI including the whole thickness of the cartilage, not taking into account spatial variations of the different layers of the cartilage [15]. It represents the mean T2 values of the whole thickness of the cartilage instead. Nevertheless, if differences in global values are demonstrated useful, it might be more practical for clinical application, because zonal studies will require a clear definition of the percentage of cartilage thickness attributable to each zone and may be prone to wider variability. The segmentation method presented in this paper is intended for practical clinical use. Current segmentation and T2 measurement methods used with research purposes need an average of 1–5 h per knee [22], unpractical for clinical routine use. Our method has been demonstrated reliable, with moderate to good intraobserver agreement. Division of the patellar cartilage into 12 locations at proximal, middle and distal levels was based in previous works that recognized that chondromalacia patellae is not a uniform pathology and may affect different parts of the cartilage with varying degrees of severity [19,20,23]. Most of the time, the marginal outer part of medial and lateral patellar facets is relatively spared, while the central middle section is most severely affected. Therefore, segmentation techniques that include the less affected parts of the cartilage might masquerade the real difference between healthy and degenerate cartilage. In summary, our work points out that an increase in T2 values of patellar cartilage occurs in early stages of degeneration. Progression of morphologic changes of chondromalacia to more severe degrees do not lead to a progressive increase of T2 relaxation times, but a tendency to stabilization or shortening of T2 approaching to basal normal values is observed. We therefore consider that T2 mapping may be useful as a way of monitoring the water content in cartilage. Strong raises of T2, mainly in central areas of cartilage, might be considered a factor of cartilage degeneration helping the clinician to decide the initiation of preventive therapies for cartilage protection. References [1] Mattila VM, Weckström M, Leppänen V, Kiuru M, Pihlajamäki H. Sensitivity of MRI for articular cartilage lesions of the patellae. Scand J Surg 2012;101:56–61. [2] Laxdal G, Kartus J, Ejerhed L, Sernert N, Magnusson L, Faxén E, et al. Outcome and risk factors after anterior cruciate ligament reconstruction: a follow-up study of 948 patients. Arthroscopy 2005;21:958–64. [3] Englund M, Lohmander LS. Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy. Arthrit Rheum 2004;50:2811–9. [4] Burstein D, Gray ML. Is MRI fulfilling its promise for molecular imaging of cartilage in arthritis. Osteoarthritis Cartilage 2006;14:1087–90.
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[5] Joseph GB, Baum T, Carballido-Gamio J, Nardo L, Virayavanich W, Alizai H, et al. Texture analysis of cartilage T2 maps: individuals with risk factors for OA have higher and more heterogeneous knee cartilage MR T2 compared to normal controls – data from the osteoarthritis initiative. Arthrit Res Ther 2011;13:R153. [6] Black C, Clar C, Henderson R, MacEachern C, McNamee P, Quayyum Z, et al. The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technol Assess 2009;13:52. [7] Post WR. Clinical evaluation of patients with patellofemoral disorders. Arthroscopy 1999;15(8):841–51. [8] Duc SR, Koch P, Schmid MR, Horger W, Hodler J, Pfirrmann CW. Diagnosis of articular cartilage abnormalities of the knee: prospective clinical evaluation of a 3D water-excitation true FISP sequence. Radiology 2007;243:475–82. [9] Stehling C, Liebl H, Krug R, Lane NE, Nevitt MC, Lynch J, et al. Patellar Cartilage: T2 values and morphologic abnormalities at 3.0-T MR imaging in relation to physical activity in asymptomatic subjects from the osteoarthritis initiative 1. Radiology 2010;254:509–20. [10] Blumenkrantz G, Majumdar S. Quantitative magnetic resonance imaging of articular cartilage in osteoarthritis. Eur Cell Mater 2007;13:75–86. [11] Bland JM, Altman DG. A note on the used of the intraclass correlation in the evaluation of agreement between two methods of measurement. Comput Biol Med 1990;20:337–40. [12] Park E, Cho M, Chang-Seok K. Correct use of repeated measures analysis of variance. Korean J Lab Med 2009;29:1–9. [13] Dunn TC, Lu Y, Jin H, Ries MD, Majumdar S. T2 relaxation time of cartilage at MR imaging: comparison with severity of knee osteoarthritis. Radiology 2004;232(2):592–8. [14] Choi JA, Gold G. MR imaging of articular cartilage physiology. Magn Reson Imaging Clin N Am 2011;19(2):249–82.
[15] Mosher TJ, Dardzinski BJ, Smith MB. Human articular cartilage: influence of aging and early symptomatic degeneration on the spatial variation of T2-preliminary findings at 3 T. Radiology 2000;214(1): 259–66. [16] Nissi MJ, Toyras J, Laasanen MS, Rieppo J, Saarakkala S, Lappalainen R, et al. Proteoglycan and collagen sensitive MRI evaluation of normal and degenerated articular cartilage. J Orthop Res 2004;22:557–64. [17] Apprich S, Welsch GH, Mamisch TC, Szomolanyi P, Mayerhoefer M, Pinker K, et al. Detection of degenerative cartilage disease: comparison of highresolution morphological MR and quantitative T2 mapping at 3.0 Tesla. Osteoarthr Cartilage 2010;18:1211–7. [18] Koff MF, Amrami KK, Kaufman KR. Clinical evaluation of T2 values of patellar cartilage in patients with osteoarthritis. Osteoarthr Cartilage 2007;15(2):198–204. [19] Hunt N, Sanchez-Ballester J, Pandit R, Thomas R, Strachan R. Chondral lesions of the knee: a new localization method and correlation with associated pathology. Arthroscopy 2001;17(5):481–90. [20] Fulkerson JP. Disorders of the patellofemoral joint. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004. p. 239–53. [21] Marticke JK, Hösselbarth A, Hoffmeier KL, Marintschev I, Otto S, Lange M, et al. How do visual, spectroscopic and biomechanical changes of cartilage correlate in osteoarthritic knee joints? Clin Biomech 2010;25:332–40. [22] Stehling C, Baum T, Mueller-Hoecker C, Liebl H, Carballido-Gamio J, Joseph GB, et al. A novel fast knee cartilage segmentation technique for T2 measurements at MR imaging e data from the Osteoarthritis Initiative. Osteoarthr Cartilage 2011;19:984–9. [23] Insall J, Falvo KA, Wise DW. Chondromalacia Patellae: a prospective study. J Bone Joint Surg Am 1976;58(1):1–8.
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
T2 mapping in patellar chondromalacia Fernando Ruiz Santiago a,∗ , Rocío Pozuelo Calvo b , Julio Almansa López c , Luis Guzmán Álvarez a , María del Mar Castellano García a a b c
Department of Radiology, Traumatology Hospital, University Hospital Virgen de las Nieves, Granada, SPAIN Department of Rehabilitation and Physical therapy, Traumatology Hospital, University Hospital Virgen de las Nieves, Granada, SPAIN Department of Physic, University Hospital Virgen de las Nieves, Granada, SPAIN
a r t i c l e
i n f o
Article history: Received 26 September 2013 Received in revised form 16 February 2014 Accepted 7 March 2014 Keywords: Chondromalacia patellae Cartilage Magnetic resonance imaging T2 relaxation time T2 mapping
a b s t r a c t Objective: To study the correlation between the T2 relaxation times of the patellar cartilage and morphological MRI findings of chondromalacia. Methods: This prospective study comprises 50 patients, 27 men and 23 women suffering of anterior knee pain (mean age: 29.7, SD 8.3 years; range: 16–45 years). MRI of 97 knees were performed in these patients at 1.5 T magnet including sagittal T1, coronal intermediate, axial intermediate fat sat and T2 mapping. Chondromalacia was assessed using a modified version of Noyes classification. The relaxation time, T2, was studied segmenting the full thickness of the patellar cartilage in 12 areas: 4 proximal (external facet–proximal–lateral (EPL), external facet–proximal–central (EPC), internal facet–proximal–central (IPC), internal facet–proximal–medial (IPM), 4 in the middle section (external facet–middle–lateral (EML), external facet–middle–central (EMC), internal facet–middle–central (IMC), internal facet–middle–medial (IMM) and 4 distal (external facet–distal–lateral (EDL), external facet–distal–central (EDC), internal facet–distal–central (IDC), internal facet–distal–medial (IDM). Results: T2 values showed a significant increase in mild chondromalacia regarding normal cartilage in most of the cartilage areas (p < 0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM. Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistical significant differences in comparison with normal cartilage, except in EMC and IMC, where similar values as mild chondromalacia were maintained (p < 0.05). Conclusions: Steepest increase in T2 values of patellar cartilage occurs in early stages of patellar cartilage degeneration. Progression of morphologic changes of chondromalacia to more severe degrees is associated to a new drop of T2 relaxation times approaching basal values in most of the areas of the patellar cartilage, except in the central area of the middle section, where T2 values remain increased. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Chondromalacia is a pathological condition of articular cartilage. In early stages of chondromalacia cartilage is softened, swollen or fibrillated; fragmentation, fissuring and subchondral bone abnormalities are present in advanced stages. Clinical findings are not reliable indicators for its diagnosis because many cases are asymptomatic. Morphological MRI, one of the preferred methods for studying articular cartilage lesions, is highly sensitive for detecting severe cartilage lesions, but its sensitivity is low for mild or incipient injury [1]. Physiologic MRI includes sequences that examine cartilage composition and increase sensitivity for early
∗ Corresponding author. Tel.: +34 627633829. E-mail address: [email protected] (F. Ruiz Santiago). http://dx.doi.org/10.1016/j.ejrad.2014.03.007 0720-048X/© 2014 Elsevier Ireland Ltd. All rights reserved.
cartilage degeneration. Early detection of cartilage injury is important because it may explain patients’ symptoms and influence short and long-term outcomes [2,3]. Quantitative T2 mapping has been reported as a technique to study the compositional integrity of cartilage. Increased cartilage T2 relaxation times have been associated with matrix damage, specifically with the loss of collagen integrity and the increase of water content. However, the role of T2 mapping at different stages of cartilage degeneration is not well defined [4]. Studies performing laminar analysis of cartilage in the knee have shown that the outer layers (articular surface layers) have higher T2 values than the basal bone surface layers. As the cartilage degenerates, the outer layer is eventually lost (falls off), therefore bringing mean values back down [5]. In this paper we try to correlate the T2 relaxation times of the patellar cartilage with morphological MRI findings of chondromalacia. Relating T2 values of cartilage to current staging of
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chondromalacia would strengthen the clinical usefulness of T2 mapping, increasing the role of MRI monitoring cartilage lesions and therapy effects [6]. 2. Methods 2.1. Subjects and study design This prospective study comprises 50 patients, 27 men and 23 women recruited during 2011 (mean age: 29.7, SD 8.3 years; range: 16–45 years). They presented uni or bilateral anterior Knee pain. All patients provided informed consent to participate in the study, which was approved by the institutional review board. Inclusion criteria were: age between 15 and 45 years and patellofemoral pain during at least 3 months, on either knee. Exclusion criteria were: history of previous knee surgery and the presence of clinical signs or imaging findings of articular narrowing, osteophytes, tendonitis, and meniscal or ligament injury. Pain was assessed using a visual analogue scale (VAS). Time of evolution and pain characteristics were registered, including the influence of activities that flex the knee, such as walking, running, prolonged sitting, squatting and ascending or descending stairs. Physical exam was performed in the rehabilitation department at the recruitment site. The physical exam included observation of static alignment of the lower extremity, evaluation of the range of motion, palpation of patellar and adjacent patellar structures, strength evaluation and special tests, such as patellar tilt, patellar compression, eccentric step and patellar apprehension tests [7]. According to physical and radiological findings knees were classified as asymptomatic, pain associated to instability or idiopathic patellofemoral pain. 2.2. Imaging studies All patients underwent MRI of both knees, even asymptomatic knees, except three of them in whom only the symptomatic knee was studied. That accounts for the 97 knees included in this study. MRI was performed at 1.5 T machine (HDx; GE Healthcare Systems, Wisconsin) using a quadrature transmit-receive coil. This included sagittal T1 (TR: 500 ms; TE: 9.5 ms); coronal intermediate (TR: 1.880 ms; TE: 44.6 ms) and axial intermediate fat sat (TR: 2.200 ms; TE: 41.4 ms) weighted images. The last sequence, T2 mapping, consisted in a multi-slice multi-echo fast spin echo (FSE) pulse sequence acquired across the length of the patella. Eight echo images were acquired at each slice location (TR: 1.000 ms; TE: 7.8, 15.7, 23.6, 31.4, 39.3, 47.2, 55.1 and 62.9 ms; FOV: 14; matrix: 256 × 160; thickness: 3 mm; gap: 0.6 mm). 9 slices per patella were procured (Fig. 1).
Fig. 1. An ROI was placed in12 locations: external–proximal–lateral external–proximal–central (EPC), internal–proximal–central (EPL), internal–proximal–medial (IPM), external–middle–lateral (IPC), external–middle–central (EMC), internal–middle–central (EML), internal–middle–medial (IMC), (IMM), external–distal–lateral (EDL), external–distal–central (EDC), internal–distal–central (IDC), internal–distal–medial (IDM). Global ANOVA values for each location are shown.
The relaxation time, T2, was studied segmenting the patellar cartilage in 12 areas (Fig. 1): 4 proximal (external facet–proximal–lateral (EPL), external facet–proximal–central (EPC), internal facet–proximal–central (IPC), internal facet–proximal–medial (IPM)), 4 in middle section (external facet–middle–lateral (EML), external facet–middle–central (EMC), internal facet–middle–central (IMC), internal facet–middle–medial (IMM)) and 4 distal (external facet–distal–lateral (EDL), external facet–distal–central (EDC), internal facet–distal–central (IDC), internal facet–distal–medial (IDM)). The central line was traced between the central crest of the bone separating both facets and the central crest of the cartilage covering the bone. Therefore, the segmented areas were symmetrical in Wiberg type I patella and asymmetrical in types II and III, where external areas are greater than internal areas, according to the size of its respective facets. The global T2 value was calculated by manually placing a region of interest (ROI) that covered the full thickness of patellar cartilage in each location. It was accomplished by simultaneously examining the T2 map and the anatomic sequence (in neighboring image panels) with synchronized cursor, slice number and zoom. First at all, the middle line slice was chosen and then, the central slice of the proximal and distal half of the patellar cartilage was selected and segmentation at the three slices performed as shown in Fig. 1. T2 relaxation time was calculated by fitting an exponential function to the signal intensity at different echo times as follows: SI (TE) ∼ exp (–TE/T2), where SI (TE) is signal intensity as a function of echo
2.3. Image analysis For the sake of consistency, chondral injuries were assessed by an experimented musculoskeletal radiologist (20 years) using a modified version of the Noyes classification system of articular cartilage defects of the knee joint [8]: grade 0, intact cartilage with normal signal and uniform thickness; grade I, focal abnormal signal without surface abnormalities; grade II, superficial ulceration or fissuring, with a depth of no more than 50% of cartilage thickness; grade III, deep ulceration or fissuring of more than 50% but less than a 100% of cartilage thickness; grade IV, full-thickness cartilage defect with edema or erosion of subchondral bone. If different grades of cartilage lesions were present, the worst lesion was used for grading the severity of affectation of patellar cartilage (Fig. 2). For statistical analysis, chondromalacia grades I and II were regrouped as mild and grades III and IV as severe.
Fig. 2. Chondromalacia grade I (A), II (B), III (C) and IV (D) of Noyes modified.
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Table 1 Association between clinical diagnosis and the presence of chondromalacia. No statistical differences were found (P = 0.051). Clinical diagnosis Cartilage
Asymptomatic
Instability
Idiopatic pain
Total
Normal Mild chondromalacia Severe chondromalacia Total
20 3 5 28
10 10 6 26
20 9 14 43
50 22 25 97
time, TE is echo time, and T2 is the transverse relaxation time [9]. T2 is defined as the time at which the signal decays to 37% of maximum signal [10]. 2.4. Statistical analysis To avoid interobserver errors, a musculoskeletal radiologist made all measurements unaware of final clinical diagnosis. To estimate intraobserver error, we randomly chose 16 knees to be measured by the same examiner on successive days. This measurement error was calculated by the coefficient of intraclass correlation [11]. For statistical analysis each knee was considered as independent. Comparison of T2 relaxation times in different quadrants between knees with different grades of chondromalacia and without chondromalacia was performed by repeated measures analysis of variance (ANOVA) [12]. Bonferroni test was performed when statistical significance was achieved in ANOVA tests. Statistical software SPSS version 15 was used. Power is the probability that if a difference exists, we find it. It was determined based on one way ANOVA analysis and calculated using a type I error of 0.05, considering the mean T2 values in each area according to the degree of chondromalacia, the percentage of knees in each group and the conjoined standard deviation of groups. Ene 3.0 software was used. 3. Results
Fig. 3. Graphic depicting the evolution of T2 relaxation values with different stage of patellar cartilage chondromalacia. EPL: external–proximal–lateral; IPC: internal–proximal–central; IPM: internal–proximal–medial; external–middle–lateral; EMC: external–middle–central; IMC: EML: internal–middle–central; EDC: external–distal–central.
3.4. Relationship between changes in cartilage T2 and severity of patellar chondromalacia Comparison of T2 relaxation values in each patellar cartilage quadrant of patients without chondromalacia versus patients with mild and severe chondromalacia was performed. Global Anova results are indicated in Fig. 1. Bonferroni post hoc multiple comparison results are depicted in Table 2 and Fig. 3. T2 values showed a significant increase in mild chondromalacia with regard normal cartilage in all quadrants (p < 0.05), except in the internal distal facet (IDC and IDM), EPC, EDL, and IMM (mean: 2.3 ± 0.3 ms; median: 2.35 ms; range: 0.9 ms (IDM)–4.0 ms (IPM)). Severe chondromalacia was characterized by a fall of T2 relaxation times with loss of statistically significant differences with regard to normal cartilage, except in EMC and IMC, where it maintained similar values as mild chondromalacia (p < 0.05).
3.1. Patients’ clinical features
4. Discussion
Of 97 analysed Knees, 28 were asymptomatic, 26 diagnosed as pain secondary to instability and 43 as idiopathic patellofemoral pain. Mean value of VAS score in symptomatic knees was 4.3 ± 0.3 and mean length of pain was 49.5 ± 5.7 months. No statistical differences were found when these parameters were compared between different clinical diagnoses.
The transverse relaxation time constant, T2, of articular cartilage has been proposed as a biomarker for cartilage integrity. There is good evidence that T2 mapping is useful for identifying sites of early-stage degeneration (early disruption of the collagen matrix) in cartilage, which appears as areas with T2 higher than that of normal cartilage [13]. This is due to increased permeability of the matrix, which leads to increased content and motion of water. Some studies show elevated T2 not only in areas of cartilage damage but also in adjacent areas, suggesting exposure of additional hydrophilic sites close to the injured cartilage areas leading to fluid accumulation and a lengthening of T2 relaxation time [14]. There has not been established any linear relationship between T2 values and osteoarthritis grades that could aid in the differentiation between mild and more severe disease. In a previous study, it was demonstrated that increase of T2 relaxation times of tibial and femoral cartilage correlate with severity of osteoarthritis (OA), but similar T2 values for subjects with moderate and severe OA were found [13]. It was hypothesised that water motility is increased in degenerated cartilage, lengthening relaxation times. Nevertheless, although our work agrees with this by demonstrating no further increase of T2 values with progression of the chondromalacia, a T2 relaxation time shortening tendency has been observed as a novel datum in severe chondromalacia, approaching that of normal cartilage in some areas. This shows that increased water content
3.2. Prevalence of chondromalacia and relationship with clinical diagnosis With regard to the presence of cartilage lesions, 50 knees were considered normal (grade 0), while chondromalacia of the patella was diagnosed in 47 knees, 22 as mild (7 grade I, 15 grade II) and 25 as severe (5 grade III, 20 grade IV) chondromalacia. Association between clinical diagnosis and the presence of chondromalacia is shown in Table 1. 3.3. Measurement error The intraclass correlation of intraobserver measurements ranged from the lower value at the IMM localization (0.632, moderate agreement) to the greater value at IDC localization (0.953, excellent agreement).
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Table 2 T2 relaxation values of areas of patellar cartilage with significant results after Bonferroni test. Power of the test in each area is shown. Values are expressed as mean ± standard error of the mean. N: normal cartilage; MC: mild chondromalacia; SC: severe chondromalacia; EPL: external–proximal–lateral; IPC: internal–proximal–central; IPM: internal–proximal–medial; EML: external–middle–lateral; EMC: external–middle–central; IMC: internal–middle–central; EDC: external–distal–central. Location
Normal
MC
SC
Significance
Power
EPL IPC IPM EML EMC IMC EDC
41.0 ± 0.5 41.8 ± 0.4 44.1 ± 0.7 37.4 ± 0.4 38.6 ± 0.4 39.7 ± 0.4 40.9 ± 0.6
43.4 ± 0.6 44.5 ± 0.7 48.1 ± 1.1 40.0 ± 1.0 40.9 ± 1.0 42.0 ± 1.2 44.0 ± 0.7
42.0 ± 0.6 42.3 ± 0.7 45.3 ± 0.7 39.5 ± 0.9 41.5 ± 1.0 42.8 ± 0.8 42.7 ± 1.0
P = 0.039: N versus MC P = 0.009: N versus MC P = 0.005: N versus MC P = 0.039: N versus MC P = 0.018: N versus SC P = 0.013: N versus SC P = 0.025: N versus MC
57.84 74.16 78.64 69.15 75.19 77.45 67.29
and mobility might only be a manifestation of early degenerative changes, while progression of cartilage injury is accompanied by a lost capacity to retain water by the damaged cartilage, which is redistributed to other locations. This would be in agreement with previous works that found elevation of the mean T2 values and increased heterogeneity of cartilage T2 relaxation time as indicative of early cartilage biochemical degeneration [5,15,16]. Apprich et al. found a significant increase of T2 relaxation times in femoral condyle cartilage with the presence of cartilage defect grade ≤2 using the International Cartilage Repair Society (ICSR) classification system; this is similar to that we have classified as mild chondromalacia [17]. Nevertheless, Koff et al. did no found any increase in T2 values in patellar cartilage in patients with different grades of osteoarthritis, determined in plain radiographs by the Kellgren (KL) method [18]. These last authors stated that the KL staging would detect accurately advanced stages of OA rather than the onset of the disease. Therefore, if there is a rapid change of T2 values during the onset of OA and not at later stages, differences of T2 values using a KL protocol for staging OA cannot be expected. That may fit with our results, where severe degrees of chondromalacia, even without radiographic signs of OA, are characterized by a drop or maintenance of T2 values with regard of those present in early mild cartilage degeneration. Although in the previous Stehling’s paper [9] it is stated that a significant correlation between patellar cartilage T2 values and the severity and grade of cartilage does exist, this conclusion was obtained trough a multiple linear regression analysis and the correlation coefficient value was not specified. That only indicates a linear relationship between the presence of chondromalacia and the increase of T2 values. The authors did not compare T2 values between groups of different severities of chondromalacia, but patients with and without chondromalacia. This study agrees with our findings, since we also observed that when we grouped our cohort’s mild and severe chondromalacia patients together, T2 values were higher than those of patients with normal cartilage. Chondromalacia within various areas of the patellar cartilage can be governed by different mechanisms. It is widely recognized that articular surfaces are not affected equally by chondromalacia and that certain areas are particularly prone to damage [19]. Fulkerson stated that chondromalacia along the lateral facet of the patella often relates to chronic patellar tilt and excessive lateral pressure syndrome, whereas chondromalacia of the medial facet is commonly related to patellar dislocation [20]. This trend has not been demonstrated in our work, with medial and lateral facets of the patella affected, independent of the clinical diagnosis. Nevertheless, we found that changes in T2 times are more strongly accentuated in central areas of the patellar cartilage. This finding may be in agreement with the arthroscopy review of Hunt et al. [19] that found that distal medial cartilage of the patella is less affected in idiopathic chondromalacia and lateral patellar maltracking. Therefore, in clinical practice, T2 values must be interpreted in combination with morphological findings. Strong rising of T2 values is associated with early chondromalacia according to Noyes’
classification; while advanced stage cartilage degeneration shows quite similar T2 values than normal cartilage in most of the cartilage surface, but can easily be diagnosed by morphological findings. The main limitation of our study is the lack of surgical confirmation of chondromalacia. Although arthroscopy is nowadays considered the gold standard for diagnosis of cartilage injury, detection of low-grade lesions with this orthopaedic technique is also difficult and the validity of this evaluation depends on the surgeon’s experience [21]. Another theoretical limitation is placement of the ROI including the whole thickness of the cartilage, not taking into account spatial variations of the different layers of the cartilage [15]. It represents the mean T2 values of the whole thickness of the cartilage instead. Nevertheless, if differences in global values are demonstrated useful, it might be more practical for clinical application, because zonal studies will require a clear definition of the percentage of cartilage thickness attributable to each zone and may be prone to wider variability. The segmentation method presented in this paper is intended for practical clinical use. Current segmentation and T2 measurement methods used with research purposes need an average of 1–5 h per knee [22], unpractical for clinical routine use. Our method has been demonstrated reliable, with moderate to good intraobserver agreement. Division of the patellar cartilage into 12 locations at proximal, middle and distal levels was based in previous works that recognized that chondromalacia patellae is not a uniform pathology and may affect different parts of the cartilage with varying degrees of severity [19,20,23]. Most of the time, the marginal outer part of medial and lateral patellar facets is relatively spared, while the central middle section is most severely affected. Therefore, segmentation techniques that include the less affected parts of the cartilage might masquerade the real difference between healthy and degenerate cartilage. In summary, our work points out that an increase in T2 values of patellar cartilage occurs in early stages of degeneration. Progression of morphologic changes of chondromalacia to more severe degrees do not lead to a progressive increase of T2 relaxation times, but a tendency to stabilization or shortening of T2 approaching to basal normal values is observed. We therefore consider that T2 mapping may be useful as a way of monitoring the water content in cartilage. Strong raises of T2, mainly in central areas of cartilage, might be considered a factor of cartilage degeneration helping the clinician to decide the initiation of preventive therapies for cartilage protection. References [1] Mattila VM, Weckström M, Leppänen V, Kiuru M, Pihlajamäki H. Sensitivity of MRI for articular cartilage lesions of the patellae. Scand J Surg 2012;101:56–61. [2] Laxdal G, Kartus J, Ejerhed L, Sernert N, Magnusson L, Faxén E, et al. Outcome and risk factors after anterior cruciate ligament reconstruction: a follow-up study of 948 patients. Arthroscopy 2005;21:958–64. [3] Englund M, Lohmander LS. Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years after meniscectomy. Arthrit Rheum 2004;50:2811–9. [4] Burstein D, Gray ML. Is MRI fulfilling its promise for molecular imaging of cartilage in arthritis. Osteoarthritis Cartilage 2006;14:1087–90.
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