European Radiology https://doi.org/10.1007/s00330-018-5466-3
MUSCULOSKELETAL
Meniscal pathologies on MRI correlate with increased bone tracer uptake in SPECT/CT Jan Rechsteiner 1 & Michael T. Hirschmann 1 & Milos Dordevic 1 & Anna L. Falkowski 2,3 & Enrique A. Testa 1 & Felix Amsler 4 & Anna Hirschmann 3 Received: 3 February 2018 / Revised: 11 March 2018 / Accepted: 6 April 2018 # European Society of Radiology 2018
Abstract Objectives To assess the relationship of subchondral bone tracer uptake (BTU) on SPECT/CT and meniscal pathologies on MRI in patients with painful knees. Methods Twenty-five patients who had MRI and SPECT/CT within 3 months without knee surgery or grade ≥3 cartilage lesions were prospectively included. Maximum values of each subchondral femorotibial area were quantified and a ratio was calculated in relation to a femoral shaft reference region, which represented the BTU background activity. Meniscal lesions were graded (intact/degeneration/tear) and meniscal extrusion (no/yes) was assessed using MRI by two musculoskeletal radiologists blinded to the SPECT/CT findings. One-tailed Spearman correlations served for statistics (p < 0.05). Results Knees with meniscal degeneration or tear showed a significantly higher BTU in the medial femorotibial compartment (p = 0.045) when compared to intact menisci. Meniscal degeneration was associated with an increased BTU in the lateral femorotibial compartment; however, this was not statistically significant (p = 0.143). Patients with an extruded meniscus showed significantly higher BTU compared to a non-extruded meniscus (p < 0.020). Conclusions Medial femorotibial BTU in SPECT/CT was associated with meniscal pathologies. Highest BTU was found in patients with meniscal tears. SPECT/CT appears to be a useful imaging modality to identify patients with overloading or early osteoarthritis. Key Points • Meniscal degeneration and tears correlate significantly with increased BTU using SPECT/CT. • Medial meniscus extrusion is associated with an increased BTU in SPECT/CT. • SPECT/CT allows detection of overloading and early osteoarthritis. Keywords Single photon emission computed tomography/computed tomography . Meniscus . Knee injuries . Osteoarthritis . Magnetic resonance imaging
Jan Rechsteiner and Michael T. Hirschmann contributed equally to this work. * Anna Hirschmann
[email protected] 1
Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland Bruderholz, 4101 Binningen, Switzerland
2
Department of Radiology, Kantonsspital Baselland Bruderholz, 4101 Binningen, Switzerland
3
Department of Radiology and Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
4
Amsler Consulting, Gundeldingerrain 111, 4059 Basel, Switzerland
Abbreviations BTU Bone tracer uptake ICC Intraclass correlation coefficient OA Osteoarthritis SPECT Single photon emission computerised tomography CT Computerised tomography MRI Magnetic resonance imaging
Introduction Loss of meniscus function, such as meniscal extrusion or loss of meniscal tissue, is known to lead to a multi-fold increase of
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peak and average contact stress in the knee joint [1–3]. Clinically, this is common in patients with degenerative meniscal lesions who undergo a partial meniscectomy or an even more devastating subtotal meniscectomy. It has been shown that loss of meniscal tissue is a key factor for development or progression of osteoarthritis (OA) [4, 5]. Furthermore, increased contact stress due to loss of meniscal tissue represents a promotor for onset and progression of early OA. Treatment of meniscal lesions has experienced some crucial improvements in the last decades. Treatment shifted from subtotal and partial meniscectomy in the past to more meniscus preserving strategies nowadays, such as meniscal suturing and transplantation [6]. Although the clinical evidence for a relationship between meniscal loss and knee overloading, as well as early OA, already exists, the direct in vivo effect of meniscal integrity on subchondral joint loading has hardly been studied so far [5]. Single photon emission computerised tomography (SPECT)/computerised tomography (CT) is a clinically useful tool to identify early OA, which is reflected by increased bone tracer uptake (BTU) representing in vivo loading of the joint. SPECT/CT is able to visualise and quantify subchondral bone overloading, which precedes joint space narrowing in OA [6–8]. It was our primary hypothesis that knees with intact menisci and those with degenerated or torn menisci differ in terms of
Fig. 1 Localisation and measurement scheme used for analysis of MRI and SPECT/CT for both the medial and lateral femorotibial compartments. The reference region (R) of the femoral shaft 10 cm above the joint line was used to calculate ratios of bone tracer uptake in the subchondral zones. AM anteromedial, IM intermediate medial, PM posteromedial
BTU in SPECT/CT; i.e. BTU is lower in knees with intact menisci than in those with meniscal lesions. The secondary hypothesis was that subchondral BTU is higher in patients with an extruded meniscus. Lastly, we hypothesised that the mechanical leg alignment influences the BTU. Thus, the purpose of this study was to assess the relationship of subchondral BTU in SPECT/CT and the presence of meniscal pathologies in magnetic resonance imaging (MRI) in patients with knee pain.
Materials and methods Sixty-three consecutive patients with knee pain undergoing SPECT/CT and MR were included in this retrospective study after approval by the local ethical committee (EK 228/13). Inclusion criteria were MRI and SPECT/CT scans within 3 months between August 2009 and February 2013. Patients with previous intra-articular surgery of the knee joint were excluded. This patient population was included in a prior, already published study [9]. The prior article dealt with cartilage lesions and bone marrow oedema in 63 patients, whereas in this manuscript we report on meniscal lesions and leg alignment. Patients (n = 38) with cartilage lesions of grade ≥3 according to modified Noyes’ grading scale on MRI were excluded [10]. The final cohort in this manuscript comprised
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25 patients with a mean age ± standard deviation of 44 ± 12 years (range, 19-67 years). There were eight women with a mean age of 43 ± 13 years (range, 24-67 years) and 17 men with a mean age of 45 ± 12 years (range, 19–64 years). Two patients had bilateral knee pain and scans, all others unilateral knee pain. MRI and SPECT/CT scans were prospectively obtained. For analysis and comparison of both imaging modalities a specific localisation scheme was used, which divided the knee into biomechanically relevant zones and allowed clear demarcation of the anterior and posterior femoral zones (Fig. 1). At this, parallel lines along the anterior and posterior femoral diaphyseal cortices served as delineation for both zones. The femorotibial joint was divided into ten zones: six tibial and four femoral zones. Only the subchondral zones were analysed. The patellofemoral joint was not considered in this study.
SPECT/CT SPECT/CT was performed using a hybrid system, including a double-head gamma-camera (Symbia T16; Siemens Healthcare, Erlangen, Germany) equipped with a pair of low-energy, high-resolution-collimators (tube voltage, 130 kV; tube current, 80 mAs/slice; pitch factor, 1.2; CTDIvol, 8.3 mGy; effective dose, 3.5 mSv; matrix, 128 × 128; reconstruction thickness, 0.75 mm; reconstruction increment, 0.5 mm). All patients received a 500-MBq technetium-99m hydroxymethane diphosphonate injection (manufacturer, CIS Bio International, Paris, France; permission-holder, CBI Medical Products Vertriebs, Schöftland, Switzerland). All SPECT images were obtained in a 128 × 128 matrix in 32 angular steps of 25 s each. Two to three hours after injection, delayed phase three-dimensional (3D) scintigraphic images (SPECT) were obtained. CT of the femoral head and ankle (3 mm slice thickness) and the knee (0.7 mm slice thickness) were acquired. For each zone, the BTU in SPECT/CT was determined twice with regards to the localisation scheme by two independent observers with 1 year of expertise in SPECT/CT analysis (Fig. 1). Between each measurement there was an interval of 6 weeks. The observers were blinded to their own previous results as well as to the results of the other observer. For volumetric quantification of BTU in a 3D data set and anatomical localisation of increased BTU, a customised previously validated software (Introspect©) was used [11]. Maximum values (mean ± standard deviation) for each area of the localisation scheme were recorded as well as normalised values for intensity of SPECT/CT tracer uptake calculated. For normalisation, the midpoint of the femoral shaft 10 cm above the joint line was used as a reference region, as previously published [11] (Fig. 1). Thus, obtained ratios were dimensionless and comparable. Furthermore, the mechanical
Table 1 Relative bone tracer uptake (BTU) of the respective subchondral bone with regards to meniscal lesions at MRI Medial meniscus
Femoral BTU
Tibial BTU
Intact
1.33 ± 0.51
1.33 ± 0.76
Degeneration
1.56 ± 0.77
1.80 ± 1.01
Tear p value
2.33 ± 0.89 0.047
2.29 ± 0.85 0.051
Intact Degeneration
1.53 ± 0.83 1.99 ± 0.77
1.37 ± 0.63 1.49 ± 0.42
p value
0.143
0.195
Lateral meniscus
Data of BTU are mean values ± standard deviations No tear was found at the lateral meniscus
leg alignment was measured in degrees on SPECT/CT using the above-mentioned software [11]. For this purpose, the mechanical alignment was determined by a line connecting the femoral head centre, the centre of medial and lateral femoral epicondyles, the centre of the tibial plateau and the talar centre.
MRI All MRI examinations were performed by using a 3-T magnet (Philips Healthcare) and a phased-array extremity coil. Proton density-weighted fat-saturated (FS) sequences in sagittal (repetition time/echo time, 1,818/30 ms; section thickness, 3 mm; field of view, 512 mm; acquisition time, 3 min 11 s), coronal (repetition time/echo time, 1,693/30 ms; section thickness, 3 mm; field of view, 448 mm; acquisition time, 3 min 26 s) and axial planes (repetition time/echo time, 1,557/30 ms; section thickness, 3 mm; field of view, 512 mm; acquisition time, 3 min 37 s), as well as T1-weighted sequence in the coronal Table 2 Relative bone tracer uptake (BTU) of the respective subchondral bone with regards to medial meniscal lesions at MRI Meniscal body
Femoral BTU
Tibial BTU
Intact Degeneration
1.35 ± 0.6 1.64 ± 0.71
1.36 ± 0.79 2.00 ± 1.06
Tear p value Posterior meniscal horn Intact Degeneration Tear p value
2.65 ± 0.61 0.010
2.63 ± 0.46 0.005
1.31 ± 0.48 1.67 ± 0.84 2.33 ± 0.89 0.027
1.28 ± 0.71 2.01 ± 1.05 2.29 ± 0.85 0.022
Data of BTU are mean values ± standard deviations The anterior meniscal horn was not included, as only one tear was found in this location
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plane (repetition time/echo time, 453/11 ms; section thickness, 3 mm; field of view, 140 mm; acquisition time, 3 min 58 s), were used for grading of meniscal lesions. MRI scans were analysed by two experienced musculoskeletal radiologists with 9 and 4 years of experience, respectively, blinded to the results of SPECT/CT analysis. The meniscus was divided into three parts (anterior horn, body and posterior horn) and graded as follows: intact (homogenous signal intensity in T1-weighted and proton density-weighted FS sequences), degeneration (signal abnormality not reaching the articular surface of the meniscus) and tear (signal abnormality unequivocally reaching the articular surface of the meniscus in at least two adjacent images) [12]. Extrusion of the meniscus was noted if greater than 3 mm [13].
Statistical analysis Data were analysed using SPSS 13.0 (SPSS). The inter- and intra-observer reliabilities of the localisation scheme for assessment of BTU in SPECT/CT as well as the inter-observer reliabilities for meniscal lesions and extrusion on MRI was determined by calculating the average measures intraclass correlation coefficients (ICC). An ICC value of 1 indicates perfect reliability, 0.81-1 very good reliability, 0.61-0.80 good reliability and 0.41-0.60 moderate reliability [14]. Because the scales for meniscal lesions and extrusion and mechanical leg alignment were not interval scaled and the assumption of normal distribution for BTU data were not fulfilled, non-parametric Spearman correlations (rho) were used. A one-sided p value of 3 times the height of the box. Post hoc power analysis (G*Power 3.1.9) showed that with the given n of 25 and a one-sided p value 3 times the height of the box)
(p = 0.020) sides, compared to knees without meniscal extrusion (Tables 3 and 4; Figs. 5 and 6). No extrusion was found for the lateral meniscus.
The mechanical alignment was distributed equally in our patient cohort: nine each showed varus and valgus alignment. In seven patients, the alignment measurements were not
Fig. 3 a Coronal (1,693/30 ms) and c sagittal (1,818/30 ms) proton density-weighted fatsaturated MR images of a 55year-old man reveal medial meniscal degeneration on the right side and corresponding bone tracer uptake (ratio, 2.67 femoral / 3.89 tibial) on b coronal and d sagittal reformatted SPECT/CT images
Eur Radiol Fig. 4 a Coronal (1,693/30 ms) and c sagittal (1,818/30 ms) proton density-weighted fatsaturated MR images from a 43year-old woman reveal a horizontal meniscal tear of the medial posterior horn on the right side with focal tibial bone marrow oedema and corresponding increased bone tracer uptake (ratio, 2.84 femoral / 3.55 tibial) on b coronal and d sagittal reformatted SPECT/CT images. Notice also bone marrow oedema (a) and increased bone tracer uptake (b) at the intercondylar notch
possible due to missing scans of the hip and ankle. The mechanical alignment of the respective leg revealed no correlation on subchondral BTU (p > 0.418-0.899). For BTU measurements and leg alignment measurements in SPECT/CT, ICCs between 0.87 and 1.00 for intra-observer reliability and between 0.89 and 1.00 for inter-observer reliability were found. Inter-observer reliabilities for assessment of meniscal lesions and extrusion on MRI were 0.79-0.85 and 0.91, respectively.
condyle, most likely due to the convex shape and range of motion of the femoral condyle leading to a prone cartilage in coherence with the higher incidence of meniscal lesions on the medial side [17]. MRI is the current Bgold standard^ and preferred imaging modality for assessing menisci, with a sensitivity and specificity for meniscal pathologies ranging from 82 to 96% [2, 3],
Discussion The present study showed that, firstly, subchondral BTU in SPECT/CT was significantly higher in painful knees with a meniscal lesion than in knees with an intact meniscus. Secondly, subchondral BTU in SPECT/CT was significantly higher in painful knees with an extruded meniscus compared to no meniscal extrusion. Several authors previously highlighted the meniscus as a protective structure for cartilage and the subchondral bone plate [15, 16]. These authors found morphological changes in the subchondral bone plate as well as in the submeniscal cartilage in compromised menisci. In our study these findings were confirmed by increased subchondral BTU in patients with meniscal tear or degeneration and meniscal extrusion. An increased BTU was typically found in the medial femoral
Fig. 5 Box plots demonstrate significantly higher medial femorotibial subchondral bone tracer uptake in patients with medial meniscal extrusion (p = 0.014). Meniscal extrusion was not evident on the lateral side (o represents an outlier, 1.5-3 times the height of the box)
Eur Radiol Fig. 6 a Coronal (1,693/30 ms) and c sagittal (1,818/30 ms) proton density-weighted fatsaturated MR images from a 45year-old woman reveal medial meniscal extrusion on the right side and corresponding increased bone tracer uptake (ratio, 1.46 femoral / 1.08 tibial) on b coronal and d sagittal reformatted SPECT/CT images
which was underscored by high ICCs for meniscal pathologies in our study. However, in patients after meniscal repair or partial meniscectomy, it is more difficult to unambiguously identify meniscal lesions on MRI [18, 19]. MRI frequently enables early detection of meniscal lesions without any symptoms [20]. It remains unclear which of these patients with a meniscal lesion will become symptomatic at a later stage. In many of these meniscal pathologies in middle-aged or elderly patients, it is questionable if the meniscal tear is really associated with the patients` symptoms. Increased biomechanical loading of the cartilage due to malalignment, loss of meniscal integrity or meniscal extrusion along with synovitis and osteophyte formation are more likely associated with the patients’ symptoms. However, it is not only altered mechanics due to meniscal injury which provoke OA. It has been suggested that meniscal injuries are associated with dysregulation of gene expression releasing catabolic processes leading to an increased risk for OA [21]. Additionally, increasing weight in patients with meniscal degeneration are at higher risk of developing a meniscal tear [22]. Therefore, knees with meniscal degeneration or tears are at risk for premature development of OA.
Lately, quantitative MRI techniques have improved in evaluating mechanical and biochemical characteristics of cartilage beside structural changes [23, 24]. Several studies have addressed the association between T2 measurements using MRI and cartilage degeneration [24–26]. Recently, Liebl et al. [27] highlighted the possible benefit of T2 relaxation time by changes in biochemical cartilage composition for evaluation of an early OA. Park et al. [24] demonstrated the added value of quantitative cartilage assessment in patients after meniscal transplantation using T2 mapping. However, early pathologies of the subchondral bone plate on MRI for the evaluation of the onset of OA still have to be defined [28, 29]. In contrast, SPECT/CT using diphosphonate bone tracers have been shown to reflect biomechanical loading and changes in the subchondral bone plate [30]. Furthermore, BTU of the knee joint correlates significantly with biochemical markers of early OA such as serum levels of cartilage oligomeric matrix protein or osteocalcin in the synovial fluid [31]. The pattern of BTU is known to correlate with pain, subchondral bone sclerosis and osteophytes on plain radiographs [7, 32]. It is also related to osteophytes and subchondral bone marrow oedema in MRI and progression
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of OA [7]. As bone scan abnormalities precede radiographic and MRI changes of OA, it has been suggested that these open a window into the pathophysiological process [7]. In contrast to SPECT, SPECT/CT as a hybrid imaging technology, gives valuable information on alignment, joint homeostasis and structural bone changes [33–35]. Reliable BTU and leg alignment measurements with ICCs ranging from 0.87 to 1.00 were achieved by using 3D volume measurements in precise anatomical areas. The fact that patients with a meniscal lesion or extruded meniscus showed increased BTU in the adjacent bone compartment can as well be explained by altered biomechanical loading [36]. Increased biomechanical loading of a knee compartment can be due to varus or valgus alignment. Hirschmann et al. [33] have shown that intensity of SPECT/CT BTU in the medial and lateral knee compartment significantly correlated with varus or valgus alignment of the knee. Although, SPECT/CT reflects the specific loading pattern of the knee with regard to its alignment, we did not find a correlation of increased BTU and leg alignment in our patient cohort. Including only superficial cartilage lesions (< grade 3 according to Noyes) and assessing the leg alignment in a supine, non-weight-bearing position may explain differences in our results from prior published data [33]. In addition, this finding might be due to the homogeneity of patient`s cohort with regards to alignment. The second finding of the present study was that patients with an extruded meniscus showed higher subchondral BTU in the adjacent joint compartments. This is in agreement with a previous MRI study by Wang et al. [13], in which the authors investigated the relationship between meniscal extrusion, knee cartilage and subchondral bone. MRI of the symptomatic knee was performed at baseline and 24 months later. They found that meniscal extrusion predicted an increase of subchondral bone lesions and tibial plateau bone expansion in OA knees and concluded that subchondral bone changes are an early consequence of meniscal extrusion [13]. These even occur before cartilage loss. The present results demonstrate the need for an appropriate validated tool, which is able to diagnose OA in its earliest stages in order to more effectively apply specialised early treatments, such as osteotomies, targeted towards prevention of OA progression [37]. Based not only on our results, it is evident that SPECT/CT has the potential to detect early OA knees as well as knees with an increased chance for developing OA [7, 33]. Since our patients with intact menisci showed a mean ratio of BTU below 1.5, we would suggest this as the cut-off value above which pathological processes could be taking place in the knee. However, further validation of this finding is required in a larger patient cohort and a longitudinal survey to assess the performance. Recently, quantitative analysis of BTU in SPECT/CT has been introduced and first results confirmed a good correlation with visual analysis of medial knee joint OA and temporomandibular joint disorder [38, 39]. This advancing
technique has the potential to objectively assess the severity of OA and precisely monitor therapeutic approaches. Our study has several limitations to be considered, including the small sample size and the retrospective nature of this study leading to a potential selection bias. However, this study reflects a prospectively collected consecutive sample minimising a possible selection bias. Cartilage degeneration might have influenced BTU activity; therefore, only patients with no or mild cartilage lesions (grades 1 and 2) were included. Including patients with mild cartilage lesions (grades 1 and 2) might have an influence on the high but statistically significant p value of medial meniscal lesions and subchondral BTU.
Conclusions Subchondral BTU in SPECT/CT of the knee was significantly higher with meniscal degeneration or tear and with meniscal extrusion. Highest BTU values were found in patients with meniscal tears. SPECT/CT appears to be a useful imaging modality to identify patients with overloading or even early OA. Funding The authors state that this work has not received any funding.
Compliance with ethical standards Guarantor The scientific guarantor of this publication is Michael Hirschmann. Conflict of interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry Felix Amsler kindly provided statistical advice for this manuscript. Informed consent Written informed consent was waived by the Institutional Review Board (EK 228/13). Ethical approval Institutional Review Board approval was obtained (EK 228/13). Study subjects or cohorts overlap Some study subjects or cohorts have been previously reported in Dordevic et al. [9]. Methodology • prospective • diagnostic study • performed at one institution
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