Received: 31 July 2017 Revised: 16 November 2017 Accepted: 16 November 2017 DOI: 10.1111/vru.12598 O R I G I N A L I N V E S T I G AT I O N Comparison between magnetic resonance imaging, computed tomography, and arthrography to identify artificially induced cartilage defects of the equine carpal joints José Suarez Sanchez-Andrade1 Andrea S. Bischofberger2 1 Diagnostic Imaging Clinic, Vetsuisse Fac- ulty, University of Zurich, CH-8057, Zurich, Switzerland Henning Richter1 Patrick R. Kircher1 Karolin Kuhn1 Séamus Hoey3 Abstract While articular cartilage changes are considered to be one of the initial events in the pathologi- 2 Equine Hospital, Equine Department, cal cascade leading to osteoarthritis, these changes remain difficult to detect using conventional Vetsuisse-Faculty, University of Zurich, CH-8057, Zurich, Switzerland diagnostic imaging modalities such as plain radiography. The aim of this prospective, experimental, 3 School of Veterinary Medicine, University College Dublin, Dublin, Ireland Correspondence José Suarez Sanchez-Andrade, Diagnostic Imaging Clinic, Vetsuisse Faculty, University of Zurich, CH-8057, Zurich, Switzerland. Email: [email protected] methods comparison study was to compare the sensitivity of magnetic resonance imaging (MRI), magnetic resonance arthrography, computed tomography (CT), and CT arthrography in the detection of artificially induced articular cartilage defects in the equine carpal joints. Defects were created in the antebrachiocarpal and middle carpal joint using curettage by a board-certified equine surgeon. Normal articular cartilage thickness varied from a maximum of 1.22 mm at the level of the distal aspect of the radius to a minimum of 0.17 mm in the proximal articular surface of the third carpal bone. Regarding cartilaginous defect measurements the remaining cartilaginous bed range from a maximum of 0.776 mm in the partial thickness defects, and 0 mm (defect reaches the subchondral bone) when total thickness defect were made. Computed tomography and magnetic resonance imaging were performed followed by CT arthrography and magnetic resonance arthrography after antebrachiocarpal and middle carpal intraarticular contrast administration. All images were reviewed by two board-certified veterinary radiologists, both of whom were blinded to the location, presence of, and thickness of the cartilage defects. A total number of 72 lesions in nine limbs were created. Mean sensitivity for localizing cartilage defects varied between imaging modalities with CT arthrography showing the best sensitivity (69.9%), followed by magnetic resonance arthrography (53.5%), MRI (33.3%), and CT (18.1%) respectively. The addition of contrast arthrography in both magnetic resonance and CT improved the rate of cartilage lesion detection although no statistical significance was found. Computed tomographic arthrography displayed the best sensitivity for detecting articular cartilage defects in the equine antebrachiocarpal and middle-carpal joints, compared to magnetic resonance arthrography, MRI, and CT. KEYWORDS articular cartilage, carpus, direct arthrography, osteoarthritis 1 INTRODUCTION Degeneration of the articular cartilage is considered a hallmark feature of osteoarthritis but changes in the articular cartilage remain difficult In the equine industry, lameness due to joint injury and disease is the to definitively identify with radiography since this technique does not most common cause of diminished athletic function in racing horses. allow direct visualization of cartilage.2–4 Several epidemiologic studies have found that lameness due to joint Various imaging techniques have been employed in both human disease is the most significant factor responsible for inability to race and veterinary medicine in the evaluation of articular cartilage. In and loss of performance.1 Osteoarthritis is a degenerative inflamma- humans, magnetic resonance imaging (MRI) has been established as tory condition in which there is a loss of articular cartilage matrix. the standard cartilage imaging modality. Magnetic resonance imaging 312 c 2018 American College of Veterinary Radiology wileyonlinelibrary.com/journal/vru Vet Radiol Ultrasound. 2018;59:312–325. 313 SUAREZ SANCHEZ-ANDRADE ET AL . techniques have been developed and optimized to depict cartilage The use of contrast media in the detection of articular carti- morphology and allow cartilage volume quantification. The most lage defects remains controversial and results have shown conflict- widely used and accurate of these cartilage-specific sequences include ing conclusions. In horses CT, CT arthrography and MRI have been spoiled gradient-recalled echo and fast spin-echo imaging.5 Three- used to detect non-cartilaginous18 and cartilaginous changes of the dimensional T1-weighted spoiled gradient-recalled echo acquisitions distal interphalangeal and metacarpophalangeal/metatarsophalangeal provide high-resolution contiguous thin-slice images in shorter scan joints.19,20 In one study, the detection of MCP/MTP joint articular car- times than can conventional spin-echo techniques. Fat-suppressed tilage pathology was unaffected by the addition of intraarticular con- spoiled gradient-recalled echo images show high contrast between trast media to MR or CT studies.18 Conversely, one study found the bright cartilage and relatively dark fluid, bone, fat, and muscle.5 Fast sensitivity and specificity of CT arthrography to be significantly greater spin-echo imaging of cartilage benefits, in addition, from inherent compared to 3 Tesla MRI for the detection of articular cartilage defects magnetization transfer effects within normal cartilage, potentially in the MCP/MTP joint of horses.20 abnormalities.4,5 Some studies have shown that the areas supporting most of the Three-dimensional spoiled gradient-recalled echo sequences pro- stress during locomotion in the equine carpus, especially during hyper- vide high spatial resolution; however imaging time is relatively long extension, are located on antebrachiocarpal and middle carpal joints and three-dimensional spoiled gradient-recalled echo sequences and particularly the dorsal and medial aspects. The carpometacarpal are particularly sensitive to motion and susceptibility artifacts and joint remains stationary under plane axial and torsional loading and previous intraarticular surgery may produce moderate amounts of therefore has lower importance in terms of the mechanical properties susceptibility artifacts in these sequences.5 Both intermediate- and related to motion and loading.21,22 increasing the relative conspicuity of cartilage T2-weighted fast spin-echo imaging sequences, with and with- out The objective of this study was to determine the sensitivity of MRI, fat suppression, have been advocated in the assessment of articular magnetic resonance arthrography, CT and CT arthrography techniques cartilage integrity.5 Proton density–weighted and T2-weighted fast for the detection of artificially induced articular cartilage defects in SE imaging techniques are well suited for morphologic assessments of eight clinically relevant anatomic regions of the equine antebrachio- articular cartilage as well as menisci and ligamentous structures, pro- carpal and middle carpal joints. Our hypothesis was that CT arthrog- viding information of a quality comparable to that obtained in surgery. raphy and magnetic resonance arthrography techniques would show T1-weighted images show intra-substance anatomic detail of hyaline the highest sensitivity values in the detection of articular cartilage cartilage but do not provide good contrast between joint effusion lesions, followed by MRI and CT. It was furthermore hypothesized that and the cartilage surface, a shortcoming that limits their usefulness the addition of intraarticular contrast media would improve the rate in the assessment of focal cartilaginous defects.6,7 In one MRI study of the equine carpus, cartilage measurements obtained in sequences of detection of the cartilage defects compared to the nonenhanced studies. such as spoiled gradient-recalled echo with and without fat saturation techniques have shown excellent agreement with histomorphometric measurements.8 The main advantage of computed tomography (CT) 2 MATERIALS AND METHODS over MR is improved spatial and temporal resolution.9 Computed tomography is still nowadays the modality of choice for evaluation of The study was a prospective, experimental, methods comparison thin cortical bone changes or subtle calcifications. In contrast, CT has design. The distal limbs of five adult horses (one Paso Fino and four inferior soft tissues contrast resolution compared to MR9 allowing Warmbloods) with a median age of 17 years (range of 12–23 years) poor differentiation between synovial fluid and articular cartilage. were collected within 12 h of euthanasia at the Equine Hospital, The intraarticular injection of contrast media in MR and CT have Vetsuisse-Faculty, University of Zürich for reasons unrelated to the been shown to help in outlining capsular and ligamentous structures study. Since this was a cadaveric study no animal permission was as well as the joint cartilage. As such magnetic resonance arthrography needed. Sample size was reached based on a consensus of the non- and computed tomography arthrography procedures can be utilized blinded authors, who considered that 80 defects (10 joints with eight in the assessment of intraarticular ligamentous structures, menisci, defects per joint) examined by two blinded observers would result in osteochondral lesions and loose bodies.10,11 Arthrography can be per- a number with sufficient statistical power. All horses had no history formed using various different contrast media including gas, saline, iod- of lameness associated with the carpus at the time of euthanasia, this inated contrast or Gadolinium based contrast media or a combination. lack of carpal lameness was the inclusion criteria for the study. After Computed tomographic arthrography allows the cartilaginous eval- euthanasia, all limbs were isolated from the body at the level of the uation of the entire joint,12 rather than constrained to areas perpen- distal diaphysis of the radius, stored at –28◦ C, and identified with a dicular to the acquisition plane as in conventional magnetic resonance number. As required, specimens were thawed to room temperature, arthrography.13 Several studies performed in the human knee, ankle clipped, and cleaned before the arthroscopic procedure. and shoulder comparing CT arthrography techniques with magnetic resonance arthrography and arthroscopic findings have shown that CT arthrography is an accurate, sensitive and specific technique in the 2.1 Arthroscopy protocol evaluation of cartilage thickness,14,15 surface cartilage lesions, and car- Arthroscopy examination of the antebrachiocarpal and middle carpal tilage loss.16,17 joints was performed by means of a standard dorsal approach23 by 314 SUAREZ SANCHEZ-ANDRADE ET AL . a board certified veterinary surgeon (A.B.). Articular cartilage defects for the presence or absence of defects in the aforementioned locations were created with variably sized curettes (Karl StorzTM size 0 and 00) in the carpal joints. Both of the observers were blinded to the presence, and located as follows: one each at the level of the medial and lateral location, number, and the characteristics of the defects in contrast to radial facets, one each at the proximal and distal articular surfaces of the other authors. Each observer was asked to review the studies for the intermediate and radial carpal bones as well as two at the proxi- evidence of cartilaginous defects beginning with CT followed by the mal articular surface of the third carpal bone (3CB); one at the level MRI, CT arthrography, and magnetic resonance arthrography respec- of the radial facet; and another one at the level of the intermediate tively. All horses were completely randomized by means of random facet, respectively (Figure 1). Defect size, shape, and depth (full or par- permutation and anonymized for avoiding bias during the examination tial thickness) varied and were randomly determined by the surgeon. of the images. Reviewers were permitted to alter the window level and The arthroscopic portals were closed in two layers: the joint capsule width, zoom, and evaluate any of the sequences within the individual with a single cruciate suture using United States Pharmacopeia 2-0 gly- study (CT, MR, CT arthrography, or magnetic resonance arthrography). comer suture and the skin in a simple interrupted pattern using United A defect was described as a discontinuity in the surface of the articu- States Pharmacopeia 2-0 polybutester suture. Following arthroscopy lar cartilage with interruption of its smooth surface. Cartilage appear- all limbs were frozen at –28◦ C and scanned within the next 2 weeks. ance varied between the different sequences, from the hypointense appearance compared to the synovial fluid in the T2 and the proton 2.2 Imaging protocol density sequences to the slightly more hyperintense appearance compared to synovial fluid in the T1 images. In the CT arthrography images The limbs were thawed over 12–18 h and subsequently imaged using the defect was defined as a focal irregular in shape defect on the artic- a multidetector 16 Slice CT (Philips 16 Brilliance. Philips AG, Zurich, ular surface that was filled with contrast media. In the plain CT studies Switzerland) in helical mode acquisition at a 0.8 mm slice thickness, recognition of the irregularity created by the defect represented the with a pitch of 1, 120 kVp, 100 mAs, a display field of view of 250 mm, most challenging aspect. matrix of 768 × 768 and in both medium and high frequency reconstruction algorithms. Immediately post CT examination, an MRI examination of all limbs was performed using a 3 Tesla magnet (Philips Ingenia, Philips AG, Zurich, Switzerland) using a surface coil (Philips Medical Systems, Best, The Netherlands). Magnetic resonance imaging sequences, planes and acquisition parameters are summarized in Table 1. To formulate a combined contrast medium for both CT arthrography and magnetic resonance arthrography, iohexol and gadolinium were combined. For arthrography, as there is no established consensus in veterinary medicine on component contrast media concentrations, our technique was based on previously published human reference values.16 The aim was to reach a final iohexol concentration of 150 mgI/ml and gadolinium to solution ratio of 1:200. As such 300 mgI/ml iohexol (GE Healthcare. Accupaque 300 mgI/ml) was diluted in 1:1 ratio with 0.9% NaCl saline. Then, an adapted volume of gadolinium contrast based media (GE Healthcare. Omniscan 0.5 mmol/ml) was added to obtain a final gado:sol ratio of 1:200. The antebrachiocarpal and the middle carpal joints were injected with 30 and 20 ml of this mix- 2.4 Gross analysis Limbs were carefully dissected by one of the authors (J.S.S.); the distal radius and individual carpal bones were disarticulated and stored for further analysis. Thin sections were acquired through the defects of the distal radius and carpal bones using an anatomic band saw and scanned using a flatbed color image scanner (Epson Perfection V700 Photo scanner) at a resolution of 800 dpi (dots per inch). The minimal articular cartilage thickness was measured and recorded by the same author with a dedicated open source image processing software designed for scientific multidimensional image (ImageJ 2.0.0, National Institute of Health, Bethesda, MD, USA) analysis at the level of each defect (measurements represent the remaining cartilaginous bed after the arthroscopic procedure) but also the unaffected cartilage adjacent to the defect, to establish the normal cartilage thickness of the location. 2.5 Statistical analysis ture, respectively, a magnetic resonance arthrography was performed The statistical parameters included in the study were decided by con- including T1W turbo field echo three dimensional and T1W turbo sensus by two of the authors (H.R. and J.S.S.). All data were statistically spin echo sequences. Finally a CT arthrography study was conducted analyzed using a commercial software package (IBM SPSS Statistics for using the previously described CT protocol. Time elapsed between the Windows, version 21.0, IBM Corp. Armonk, NY, USA). Based on the intraarticular injection of contrast media and the magnetic resonance study design and the examined sample number, the data distribution arthrography was less than 1 min and between magnetic resonance was not assumed to be normal. Sensitivity values and 95% confidence arthrography and CT arthrography was between 5 and 10 min. interval were calculated by considering gross analysis as the reference for each of the different imaging modalities. Interobserver agreement 2.3 Image analysis was calculated by means of nonweight kappa (k) statistics. Nonparametric tests (Friedman and Wilcoxon) were performed to analyze data Images were reviewed independently by two board certified radiolo- between all modalities. P < 0.05 was considered significant. Negative gists with 7 (S.H.) and 9 (K.K.) years of experience using a diagnostic controls were not established in the study design; consequently speci- workstation (Mac OS X Yosemite. 2.66 GHz Intel Core 2 Duo. Apple, ficity, positive predictive value, negative predictive value, and accuracy CA, USA) and a dedicated medical imaging software (Horos v2.0.0 RC5) could not be calculated. SUAREZ SANCHEZ-ANDRADE ET AL . 315 F I G U R E 1 Sagittal (A) and dorsal (B) computed tomographic arthrography multiplanar reconstructed images of a defect located at the level the lateral facet of the distal articular surface of the radius (arrows) and the corresponding gross image of the sagittal section made through the defect (C). In (A) and (B) contrast media is noted within the antebrachio carpal and middle carpal joints and filling the focal indentation in the articular surface that represent the artificially performed defect. Moderate amount of air is visible within the periarticular soft tissues as well as within the carpal joints. Air was unavoidably introduced during the arthoscopic procedure [Color figure can be viewed at wileyonlinelibrary.com] 316 SUAREZ SANCHEZ-ANDRADE ET AL . TA B L E 1 Scanning parameters of the magnetic resonance imaging sequences used in the study T2W TSE PD T1W TSE T1W TFE Plane Sagittal, dorsal Sagittal Sagittal, transverse 3D Reconstructed Voxel size 0.25 × 0.31 mm 0.40 × 0.45 mm 0.25 × 0.31 mm 0.40 × 0.40 × 0.60 mm Slice thickness 1.5 mm 2.0 mm 2.0 mm 0.6 mm FOV 120 × 120 × 102 mm 120 × 120 × 107 mm 110 × 110 × 101 mm 160 × 160 × 130 mm Matrix 344 × 270 300 × 256 3126 × 250 268 × 268 TR 6950 3120 600 13 100 30 9 6 Freq offset TE 220 Hz Averages 2 3 2 1 Interslice gap 1.5 mm 2.0 mm 2.0 mm – Flip Angle 90 90 90 8 Fat Sat No SPIR No No Contrast Pre Pre Pre/Post Pre/Post TSE, turbo spin echo; PD, proton density; TFE, turbo field echo; FOV, field of view; TR, time to repeat; TE, time to echo; Fat Sat, fat saturation. 3 RESULTS between CT arthrography and MRI, and between CT arthrography and CT. A total number of 72 defects were created in the antebrachiocarpal Finally, the addition of contrast media improve lesion detection as and middle carpal joints and reviewed by the two, board-certified vet- more defects were detected in the post contrast studies compared erinary radiologists (Figures 2–6). One of the limbs was inadvertently to the plain studies (Table 2); however no statistical significance was lost during the study time period. The mean sensitivity values for found between the mean sensitivity values of all modalities, in con- each technique and the interobserver agreement for both observers trast with our second hypothesis. When results were analyzed for are summarized in the Table 2. Computed tomography arthrography observer 1, there was not a significant difference between magnetic showed the highest sensitivity in lesion detection (69.9%), followed resonance arthrography and MRI (P = 0.237), between CT and mag- by magnetic resonance arthrography (53.5%), MRI (33.3%), and CT netic resonance arthrography (P = 0.170), and between CT arthrogra- (18.1%). For both observers CT arthrography displayed the best sen- phy and magnetic resonance arthrography (P = 0.178), significant sta- sitivity for lesion detection followed by magnetic resonance arthrog- tistical differences were noted for observer 1 between CT arthrogra- raphy, MRI, and CT according to our first hypothesis. When sensitivity phy and MRI (P = 0.023) and CT arthrography and CT (P = 0.005) as results were break down for observer 1 and 2, the maximum sensitiv- well as for all modalities for observer 2. ity for lesion detection was seen also for CT arthrography (observer 1: Based on the measurements obtained with the dedicated open 55.6%, observer 2: 84.5%). In none of the techniques all lesions were source image processing software on the sagittal cuts of the carpal detected. The comparison between the gross analysis and the detec- bones and radius normal cartilage thickness varied depending on the tion rate showed high significant differences for all modalities in lesion location from a maximum height of 1.22 mm in the distal aspect of identification. Comparison between gross analysis and imaging modal- the radius to a minimum of 0.17 mm in the radial facet of the third ities was only related to the presence or absence of a lesion. carpal bone. The cartilage thickness at the created defects ranged from Friedman tests, performed to detect differences in lesion detection across multiple modalities, were highly significant (P < 0.001). 0.776 mm of the remaining cartilage bed thickness in partial-thickness defects to an absence of cartilage in full-thickness defects. Table 3 summarizes the P-values between modalities for the detection rate of the two observers. For observer 1, the comparison of detection rate between modalities showed significant differences between 4 DISCUSSION CT arthrography and MRI (P = 0.023) and between CT arthrography and CT (P = 0.005). For observer 2, significance could be detected The best results in detection of articular cartilage defects of the equine between all modalities. Agreement between MRI and magnetic res- antebrachiocarpal and middle carpal joints were achieved with CT onance arthrography was k = 0.253 (fair) for observer 1 and k = arthrography followed by magnetic resonance arthrography, MRI, and 0.264 (fair) for observer 2 respectively. Agreement between CT and CT CT in agreement with our hypothesis. arthrography was k = 0.052 (slight) for observer 1 and k = 0.136 (slight) for observer 2. The higher spatial resolution of CT arthrography associated with the high contrast between the low density of cartilage and the highly For observer 1 and 2 significance differences were noted between attenuating intraarticular iodine allows a better confidence level in modalities at several sites (Table 4). For both observers, signifi- the diagnosis of cartilage lesions compared to MRI and MR arthrog- cant differences were noted at the proximal radial carpal bones raphy. This is in agreement with previous studies in human medicine SUAREZ SANCHEZ-ANDRADE ET AL . 317 F I G U R E 2 Sagittal T1 weighted turbo field echo magnetic resonance arthrography (A) and Dorsal T2 weighted magnetic resonance imaging (B) images depicting a defect on the proximal articular surface of the third carpal bone. In (A) contrast media is visible within the periarticular soft tissues dorsal to the carpal joints as well within the antebrachio carpal and middle carpal joints filling the joints spaces, whereas in (B) the hyperintense synovial fluid highlights the lesions. An additional defect can be seen in the lateral aspect of the distal articular surface of the radius in (B) (dotted arrows). Corresponding gross (C) image of the lesion in the third carpal bone [Color figure can be viewed at wileyonlinelibrary.com] 318 SUAREZ SANCHEZ-ANDRADE ET AL . F I G U R E 3 Sagittal computed tomographic arthrography multiplanar reconstructed image (A) showing a defect on the distal articular surface of the radial carpal bone (white arrow) with its corresponding gross image (C). Dorsal computed tomographic arthrography image (B) showing two lesions; one located on the proximal articular surface of the intermediate carpal bone (black arrow) with its corresponding scanned gross image (D). The white dotted arrow highlights a defect on the proximal articular surface of the radial carpal bone. Defects are seen as focal indentations on the thin hypoattenuating line that represents the articular cartilage. The asterisk in (B) represents an artifact likely due to volume averaging since no defects were present at that location [Color figure can be viewed at wileyonlinelibrary.com] SUAREZ SANCHEZ-ANDRADE ET AL . 319 F I G U R E 4 Sagittal T1 weighted turbo fast echo magnetic resonance arthrography (A) and dorsal CTA (B) images demonstrating a defect (arrows) on the medial aspect of the proximal articular surface of the third carpal bone. Real defect thickness (C) and size (D) can be seen in the in the scanned gross images. Cartilaginous defect in this case measured 0.37 mm in thickness [Color figure can be viewed at wileyonlinelibrary.com] 320 SUAREZ SANCHEZ-ANDRADE ET AL . F I G U R E 5 Sagittal T2 weighted magnetic resonance imaging (A) and T1 weighted turbo spin echo magnetic resonance arthrography (B) images showing a defect (arrows) on the proximal articular surface of the intermediate carpal bone. One can notice the hyperintense synovial fluid in the T2 weighted image (A) and the hyperintense appearance of the contrast media in the T1 weighted image (B) filling the focal indentation on the articular surface that represents the artificially induced defect. Bottom images represent the gross scanned intermediate carpal bone, sagittal cut (C) and entire bone (D). Articular cartilage thickness adjacent to the defect was in this case 0.88 mm [Color figure can be viewed at wileyonlinelibrary.com] SUAREZ SANCHEZ-ANDRADE ET AL . 321 F I G U R E 6 Transverse computed tomography images showing the approximate location (red crosses) where the board certified surgeon performed the articular defects. Location is approximate since defects were randomly performed and defect location was not always the same in terms of laterality. One can also appreciate the gas present between the carpal bones and periarticular soft tissues introduced during the arthroscopic procedure [Color figure can be viewed at wileyonlinelibrary.com] evaluating the usefulness of CT arthrography in the assessment The low interobserver agreement displayed for all the techniques, of joints with thin articular cartilage. Furthermore CT arthrography is especially between CT arthrography and CT, as well as the low sen- considered in human medicine the most accurate method in evaluating sitivity may be explained by the several limitations of the current cartilage thickness, in the settings of research studies.14–16 In this study design and imaging modalities. In this study each observer was regard CT arthrography is more accurate than cartilage specific a board-certified radiologist with 7 and 9 years of experience in the MRI sequences such as spoiled gradient-recalled echo as well as MR evaluation of equine imaging, plus the more large animal based train- arthrography, as shown by cadaveric studies on the human ankle15 and ing of observer 1 in relation to observer 2. We must recognize that the hip,14 respectively. A statistical significant difference was found interobserver agreement is fundamentally affected by the ability of between CT arthrography and magnetic resonance arthrography (P = an observer to identify defects, which may be associated with fac- 0.002) using the same contrast media. tors such as experience and confidence in identifying subtle findings. 322 SUAREZ SANCHEZ-ANDRADE ET AL . TA B L E 2 Lesion detection (sensitivity) for all modalities (computed tomography, computed tomographic arthrography, magnetic resonance imaging, and magnetic resonance arthrography) of both observers and interobserver agreement (k) equate in further characterization of the defects into partial or full thickness in any of the imaging modalities. As such it was not feasible to analyze full- or partial thickness defects separately or make an attempt to correlate gross measurements of the cartilage with mea- CT CTA MRI MRA Observer 1 34.7% 55.6% 36.1% 45.8% our institution and with few papers in veterinary medicine describing Observer 2 1.4% 84.5% 30.6% 61.1% CT arthrography and magnetic resonance arthrography appearance of Mean Sensitivity 18.1% 69.9% 33.3% 53.5% the equine articular cartilage, therefore image interpretation of such surements from the imaging modalities. Magnetic resonance arthrog- Sensitivity raphy and CT arthrography techniques are not performed routinely at Inter-observer agreement (*) 0.052 0.136 0.253 0.264 *Significant at P < 0.05. CT, computed tomography; CTA, computed tomographic arthrography; MRI, magnetic resonance imaging; MRA, magnetic resonance arthrography. studies has some inherent difficulties. During the arthroscopic procedure a moderate amount of gas was inadvertently but unavoidably introduced into the joint space creating magnetic susceptibility artifacts in the subsequent imaging studies and thus the interpretation of the images was made more difficult compared to the more normal clini- Without separation of the adjacent articular surfaces due to intraar- cal circumstances since some of these gas bubbles may be located adja- ticular fluid administration, defect detection with CT alone seems cent to the artificially created defects and therefore obscuring them. unlikely. We choose to include CT, even knowing its limited value in Considering the ex vivo nature of this study and that after collection, all cartilage evaluation, because we decided to have pre- and postcontrast specimens were frozen for a variable period prior to imaging, it is possi- studies in CT and also in MRI. ble that postmortem change and freeze–thaw effects could have led to This low interobserver agreement in lesion detection and the low worsening of artifacts identified on cross-sectional imaging studies.28 number of limbs in the study may also explain the not significantly These artifacts include decrease contrast between different tissues differences between modalities in lesion detection. However sensi- when temperature is around 0◦ C29 or a central signal reduction arte- tivities and the degree of agreement were always the highest in the fact, resembling an isotherm distribution.30 Therefore subtle inade- postcontrast studies independently of the observer. Based on quacies in core specimen thawing can lead to an initially confusing pat- the results of the sensitivities displayed in Table 2, we postulate that tern of central signal dampening; however none of these changes were the addition of contrast media is superior to the plain studies but it is detected in any of our examinations. A combination of these reasons limited by the interobserver variation. may partially explain why the observers did not detect many of the Based on the measurements acquired adjacent to the cartilaginous lesions the normal articular cartilage thickness in the antebrachio- defects and similarly why there was a lower interobserver agreement in lesion detection. carpal and middle carpal joints is very thin, ranging from 0.17 mm The rounded conformation of the equine antebrachiocarpal and at the level of the proximal articular surface of the third carpal middle carpal joints can also act as a limiting factor in the detection of bone to 1.2 mm at the level of the radial articular facets. There- lesions. The limitations of spatial resolution of the imaging modalities fore, the spatial and contrast resolution pose a greater limitation in used, leading to volume averaging are made worse by the curved struc- the equine carpus than for other regions such as the human knee, tures. The use of unique plane images may have led to volume averag- where articular cartilage is 5–6 mm25 and thus is considerably thicker ing affecting lesion identification, except for the limited slices oriented than the cartilage of the antebrachiocarpal and middle carpal joints. perpendicular to the joint surface.31 The equine carpal joints represent Even the equine distal interphalangeal joint had areas with cartilage a more complex anatomic area compared to the distal interphalangeal two to three times thicker17 than previously reported in the equine or metacarpophalangeal joints; including thinner cartilage, a more metacarpophalangeal26 or carpal27 joints. Due to the thin cartilaginous rounded articular surface, and multiple small bones forming the joints, coverage in all equine carpal joints, differences in thickness between all of which affect the spatial resolution of MRI and CT imaging.19,26,27 partial and full-thickness defects resulted in only a few hundreds of Limitations due to cartilage thickness have been already describe in a micrometers. It is described that pixel size has to be at least three previous human study which evaluated the efficacy of MRI in detect- times smaller than the cartilage thickness to identify three cartilage ing articular cartilage defects of the wrist and conclude that MRI is rel- laminae.8,26 The achievable spatial resolution of the MRI and magnetic atively inaccurate for detecting and allowing description of focal artic- resonance arthrography sequences used in the study as well as the ular cartilage defects in the radiocarpal joint.24 As a result, we limited minimal spatial resolution of the CT protocols was considered inad- evaluation to the detection of or absence of defects and attempts at TA B L E 3 Wilcoxon signed ranks test of lesion detection between modalities for both observers CT vs. MRI CT vs. MRA Observer 1 0.862 0.170 Observer 2 <0.001* <0.001* CTA vs. CT CTA vs. MRI 0.005* 0.023* <0.001* <0.001* CTA vs. MRA MRA vs. MRI 0.178 0.237 0.002* <0.001* *Significant at P < 0.05. CT, computed tomography; CTA, computed tomographic arthrography; MRI, magnetic resonance imaging; MRA, magnetic resonance arthrography. 323 SUAREZ SANCHEZ-ANDRADE ET AL . TA B L E 4 Obs1 Obs2 Comparison between detection rate for each modality at the different locations with the P-values of comparisons between modalities MRA vs. MRI CT vs. MRI CTA vs. MRI CT vs. MRA CTA vs. MRA CTA vs. CT RAD 22.2 vs. 22.2% 44.4 vs. 22.2% 33.3 vs. 22.2% 44.4 vs. 22.2% 33.3 vs. 22.2% 33.3 × 44.4% Lat 1.000 0.317 0.655 0.317 0.655 0.564 RAD 22.2 vs. 66.7% 33.3 vs. 66.7% 55.6 vs. 66.7% 33.3 vs. 22.2% 55.6 vs. 22.2% 55.6 vs. 33.3% Med 0.102 0.257 0.655 0.655 0.083 0.317 RCB 66.7 vs. 55.6% 33.3 vs. 55.6% 100 vs. 55.6% 33.3 vs. 66.7% 100 vs. 66.7% 100 vs. 33.3% Prox 0.564 0.317 0.046* 0.083 0.083 0.014* RCB 44.4 vs. 33.3% 44.4 vs. 33.3% 55.6 vs. 33.3% 44.4 vs. 44.4% 55.6 vs. 44.4% 55.6 × 44.4% Dist 0.655 0.655 0.317 1.000 0.655 0.655 ICB 88.9 vs. 55.6% 66.7 vs. 55.6% 77.8 vs. 55.6% 66.7 vs. 88.9% 77.8 vs. 88.9% 77.8 vs. 66.7% Prox 0.180 0.655 0.414 0.317 0.564 0.655 ICB 44.4 vs. 33.3% 22.2 vs. 33.3% 44.4 vs. 33.3% 22.2 vs. 44.4% 44.4 vs. 44.4% 44.4 × 22.2% Dist 0.655 0.655 0.655 0.317 1.000 0.317 3CB 66.7 vs. 0% 11.1 vs. 0% 44.4 vs. 0% 11.1 vs. 66.7% 44.4 vs. 66.7% 44.4 vs. 11.1% Lat 0.014* 0.317 0.046* 0.025* 0.317 0.083 3CB 11.1 vs. 22.2% 22 vs. 22.2% 33.3 vs. 22.2% 22.2 vs. 11.1% 33.3 vs. 11.1% 33.3 × 22.2% Med 0.655 1.000 0.655 0.655 0.157 0.655 RAD 66.6 vs. 33.3% 0 vs. 33.3% 100 vs. 33.3% 0 vs. 66.7% 100 vs. 66.7% 100 vs. 0% Lat 0.083 0.083 0.014* 0.014* 0.083 0.003* RAD 55.6 vs. 77.8% 0 × 77.8% 88.9 vs. 77.8% 0 × 77.8% 88.9 vs. 55.6% 88.9 vs. 0% Med 0.414 0.008* 0.655 0.025* 0.180 0.005* RCB 66.7 vs. 22.2% 11.1 vs. 22.2% 100 vs. 22.2% 11.1 vs. 66.7% 100 vs. 66.7% 100 vs. 11.1% Prox 0.046* 0.655 0.008* 0.025* 0.083 0.005* RCB 44.4 vs. 33.3% 0 vs. 33.3% 100 vs. 33.3% 0 vs. 44.4% 100 vs. 44.4% 100 vs. 0% Dist 0.655 0.083 0.014* 0.046* 0.025* 0.003* ICB 77.8 vs. 22.2% 0 vs. 22.2% 100 vs. 22.2% 0 vs. 77.8% 100 vs. 77.8% 100 vs. 0% Prox 0.025* 0.157 0.008* 0.008* 0.157 0.003* ICB 88.9 vs. 22.2% 0 vs. 22.2% 88.9 vs. 22.2% 0 vs. 88.9% 88.9 vs. 88.9% 88.9 vs. 0% Dist 0.034* 0.157 0.034* 0.005* 1.000 0.005* 3CB 77.8 vs. 0% 0 vs. 0% 77.8 vs. 0% 0 vs. 77.8% 77.8 vs. 77.8% 77.8 vs. 0% Lat 0.008* 1.000 0.008* 0.008* 1.000 0.008* 3CB 11.1 vs. 33.3% 0 vs. 33.3% 11.1 vs. 33.3% 0 vs. 33.3% 11.1 vs. 11.1% 11.1 vs. 0% Med 0.157 0.083 0.157 0.083 1.000 0.317 *Significant at P < 0.05. MRI, magnetic resonance imaging; CT, computed tomography; MRA, magnetic resonance arthrography; CTA, computed tomographic arthrography; RAD, radial bone facet; RCB, radial carpal bone; ICB, intermediate carpal bone; 3CB, third carpal bone. differentiation between full and partial cartilaginous defects were not sition times at high resolution and higher sensitivity to susceptibility undertaken. artifacts.26,35 Apart from the fat saturation techniques, also the gra- The sequences in our MRI protocol were chosen as they have been dient echo MR sequences, named turbo field echo in our protocol, previously described in the literature to be effective for evaluation may have affected image interpretation. Magnetic susceptibility arti- of articular cartilage in both veterinary and human medicine.32–34 fact results in signal loss and distortion due to magnetic field inhomo- The MRI parameters are reflective of the parameters used for equine geneity and occurs at tissue interfaces, such as where bone and soft orthopedic MRI at our institution and acquisition times of all the tissue meet. sequences used here were considered acceptable for clinical use, Our study was designed for the use of a single contrast agent for since the overall time of the imaging protocol for the MRI including the all imaging modalities aiming for its use in a clinical situation regard- postcontrast was around 70 min. With short TE and a low flip angle, less of the modality employed and allowing multiple modalities to be proton density and T1 effects predominate, which result, particularly used with a single intraarticular injection. In MRI, the use of other con- cartilage.26 trast media such as saline solution may have facilitated detection of Some limitations of the fat saturation techniques include longer acqui- articular cartilage pathology in the T1 fast field echo or proton density when fat suppression is applied, in very bright hyaline 324 SUAREZ SANCHEZ-ANDRADE ET AL . sequences, as the ideal contrast agent for the sequences used would be hypointense to the articular cartilage rather than isointense.33 While it is possible to achieve similar joint distension with saline and gadolinium, the imaging characteristics of intra- articular gadolinium confer Category 2 (a) Drafting the Article: Suárez J, Hoey S, Richter H (b) Revising Article for Intellectual Content: Suárez J, Richter H, Kuhn K, Bischofberger AS, Kircher PR, Hoey S certain advantages over saline. While saline is inert and inexpensive, intraarticular saline and any intraarticular or periarticular fluid collection will be of similar signal intensities36 making the differentiation between them impossible. Some authors report an interaction Category 3 (a) Final Approval of the Completed Article: Suárez J, Richter H, between iodinated contrast and gadopentetate dimeglumine and sug- Kuhn K, Bischofberger AS, Kircher PR, Hoey S gested that iodinated contrast diminished the ability of gadopentetate dimeglumine to shorten T1 relaxation times in high concentrations.37 Jinkins et al.38 found that iodinated contrast agents themselves have a ORCID Andrea S. Bischofberger http://orcid.org/0000-0002-7623-8627 weak T1 shortening effect that results in higher signal intensity than water as seen on T1-weighted sequences, thus making the differentiation between contrast media and cartilage more difficult. Another study describes how following intraarticular injection of gadolinium and iodinated contrast, authors occasionally observed suboptimal contrast on T1-weighted images and low signal intensity of synovial fluid on T2-weighted images, both on high-field and low-field strength systems and concluded that mixture of gadolinium with iodinated contrast might affect gadolinium enhancement and reduce image quality.39 Thus it may be possible that the mixture of contrast media used with a concentration of almost 50% iodine was not ideal for the magnetic resonance arthrography studies. One study shows that a mixture of 1.25 mmol/l gadolinium and 25% iodinated contrast agent is optimal for simultaneous magnetic resonance arthrography and CT arthrography in vitro.40 They further recommend that to decrease the signal loss of additive iodine, an iodinated contrast agent concentration of more than 37.5% should not be used for simultaneous magnetic resonance arthrography and CT arthrography; however the use of lower concentrations of iodinated contrast may result in lower contrast viscosities that would enhance the delineations of small intraarticular structural irregularities.41 It is possible that altering the protocol to include modified magnetic resonance image sequence parameters, use of a different contrast media, such as saline or a lower concentration of iodine in the final mixture, may improve the utility of MRI and/or CT arthrography. 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