Contrast-enhanced dynamic and static MRI correlates with quantitative 99Tcm-labelled nanocolloid scintigraphy. Study of early rheumatoid arthritis patients

K. Palosaari, J. Vuotila1, R. Takalo, A. Jartti, R. Niemelä, M. Haapea, I. Soini1, O. Tervonen and M. Hakala1

Oulu University Hospital, Oulu and 1 Rheumatism Foundation Hospital, Heinola, Finland.

Correspondence to: K. Palosaari, Department of Diagnostic Radiology, Oulu University Hospital, Kajaanintie 50, FIN-90029, BOX 50, Oulu, Finland. E-mail: kari.palosaari{at}oulu.fi


    Abstract
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Objective. The aim of this study was to evaluate the roles of contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative 99Tcm-labelled nanocolloid (NC) scintigraphy in detecting wrist joint inflammation in early rheumatoid arthritis (RA) patients.

Methods. Twenty-eight early RA patients (median symptom duration 5 months, range 1–12 months) underwent MRI, NC scintigraphy, laboratory and clinical examinations. Static wrist MRI scans were retrospectively scored for synovitis, bone oedema and erosions by two independent readers using the recently published rheumatoid arthritis MRI scoring system (RAMRIS). Twenty NC scans were analysed quantitatively by measuring maximum 99Tcm-NC uptake in three small areas of each wrist. From the same locations on the wrists, dynamic MRI gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement rates (E-rate) were measured. The average 99Tcm-NC uptake of the whole wrist region was also measured and average E-rates were calculated. Correlations between MRI and NC scintigraphy measurements were calculated. Correlations between imaging methods of the wrist and the global measures of inflammation (laboratory and clinical examinations) were also assessed.

Results. Strong correlations emerged between maximal 99Tcm-NC uptake and MRI E-rates, reflecting similar performance of the methods in detecting local synovial inflammation. 99Tcm-NC uptake and MRI E-rate correlated with semiquantitative scoring of synovitis and bone oedema from static MRI scans. The erythrocyte sedimentation rate (ESR) correlated with MRI scores, E-rate and 99Tcm-NC uptake. No correlation between the clinical parameters and the imaging methods was detected. Inter-observer reliability for scoring synovial hypertrophy, bone oedema and bone erosions from static MR images were high (single-measure fixed-effects intra-class correlations 0.87, 0.93 and 0.91 respectively). Intra-observer reliability for E-rate and 99Tcm-NC measurements of 10 randomly picked scans was found to be high, with an intra-class correlation of 0.92; 95% confidence interval (CI) 0.84–0.96 and 0.99; 95% CI 0.98–1.00, respectively.

Conclusions. Objective information about wrist joint inflammation can be obtained with contrast-enhanced dynamic MRI and quantitative 99Tcm-labelled NC scintigraphy. MRI also allows visualization and semiquantitative scoring of bone oedema and erosions of the wrist. Dynamic MRI and NC scintigraphy are safe and easy to perform, and they can be used in a long-term follow-up of rheumatoid patients.

KEY WORDS: Dynamic MRI, NC scintigraphy, Rheumatoid arthritis


    Introduction
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Early rheumatoid arthritis (RA) is characterized by synovitis, inflammation and hypertrophy of synovial membrane tissue, which is presumably associated with subsequent cartilage destruction and bone erosion. Evaluation of the degree of synovitis is generally based on clinical examination and laboratory parameters. However, the qualitative and subjective information obtained from physical examination involves considerable inter-observer variability and bias arising from observer–patient interaction [1]. Magnetic resonance imaging (MRI) allows direct visualization of inflammatory tissue, bone oedema and erosions, and gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA)-enhanced scanning provides a tool for the assessment of inflamed synovium [2–17]. Following intravenous injection, Gd-DTPA is transported unlinked in the plasma and passes into the interstitial space, depending on the local capillary permeability and the tissue perfusion [18]. Inflamed synovium enhances rapidly after intravenous (i.v.) injection of Gd-DTPA, and registration of the time-dependent changes in the signal intensity of synovial membrane by means of fast gradient-echo techniques (dynamic MRI) has been reported to provide a potential quantitative marker of synovial inflammation [2–10]. Quantification of the volume of inflamed synovium in a rheumatoid joint has shown significant correlation with macroscopic and microscopic assessments of synovial inflammation [11]. However, manual measurement of volume is time-consuming, and various semiquantitative scoring methods for grading synovial membrane hypertrophy have been used [12–17]. Recently, the international Outcome Measures in Rheumatology group (OMERACT) published an MRI scoring system (RAMRIS) for grading synovitis, erosions and bone oedema in the wrist and metacarpophalangeal (MCP) joints [19], which was validated in several exercises [20–22]. Along with quantitative dynamic MRI scanning, we used the RAMRIS scoring system in grading synovitis, bone oedema and erosions in our study of early RA wrist joints.

Whole-body radiolabelled albumin-nanocolloid (NC) scintigraphy has proved to be an effective method for identifying patients with active peripheral joint disease [23–25], and an accurate method for quantifying nanocolloid uptake in inflamed tissue at the local joint level is available [26]. The mechanism of 99Tcm-NC uptake is not well understood, but labelled nanocolloid particles are thought to leave the circulation and to enter the extravascular compartment at sites of inflammation, where increased local vascular permeability of the synovial membrane prevails [27].

In this paper, use of 99Tcm-labelled NC scintigraphy in quantifying local joint inflammation in early RA patients is presented and the method is compared with contrast-enhanced dynamic and static MRI. The associations between methods of imaging the wrist and the global measures of inflammation (laboratory and clinical examinations) are also assessed.


    Material and methods
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Patients and clinical assessment
Twenty-eight patients with early RA fulfilling the revised American College of Rheumatology (ACR) criteria for rheumatoid arthritis were investigated [28]. Enrolment into the study took place in 2000 to 2001. The clinical assessments were made by the senior rheumatologists of our hospital as part of their routine clinical practice. Swollen joint count, tender joint count and Health Assessment Questionnaire (HAQ) score [29] were recorded. In addition, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and IgM rheumatoid factor titre were measured. MRI and NC scintigraphy were performed on the same day, a few days to weeks after the clinical assessment (range 0–11 weeks, median 4 weeks). Patient data are summarized in Table 1. Altogether 24 patients were taking disease-modifying anti-rheumatic drugs (DMARDs) before imaging, as the patients were usually started on medication immediately after the clinical assessment. All patients gave their informed consent to the protocol, which had been approved by the local ethics committee.


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TABLE 1. Patient characteristics

 
Imaging and assessment of nanocolloid scintigraphy
All patients received an intravenous injection of 555 MBq of 99Tcm-labelled nanocolloid (Nanocoll®, Nycomed Amersham Sorin, Saluggia, Italy), and anterior spot views of their hands were acquired 1 h later using an Elscint 409 ECT camera (Haifa, Israel) equipped with a low-energy general-purpose collimator. Due to technical failure in data storage, the quantitative data for eight study patients were destroyed, and we were thus able to quantitatively analyse the scans of 20 patients. Matrix size was 128 x 128 and acquisition time of the wrist joints was 10 min. The image data were transferred into a Hermes processing system (Nuclear Diagnostics, Hagerstad, Sweden) and filtered using a low-pass filter [26]. Before normalization, the 99Tcm-NC images had a low count level of some 100 kcounts. Starck and Carlsson [26] used a transmission phantom to find the type of filter most suitable for static images at various count levels. They used a 57Co flood source, and images containing 100, 350 and 1000 kcounts were acquired in a 256 x 256 matrix. They found only minor differences between the different filter types. For a low-pass filter, the cut-off frequency of 0.32 cycles/cm was the best at all count levels. Therefore, it was a logical choice for our purposes. The rescaling and measurements were chosen so that they were as objective as possible. In the rescaling operation, all the pixel values were multiplied by a constant, determined by the count level in a normal radius. The quantification was focused on the more painful or dominant wrist. The accumulation of the radiolabelled nanocolloid varied considerably within the wrist region of most patients. Therefore, maximum uptake in three different regions of interest (ROIs) of the wrist was measured (Fig. 1A). The area of the most intense uptake of the 99Tcm-NC was always included in one of the ROIs. For comparison with the clinical data and the static MRI scores, the average uptake of the whole wrist region was also measured. The filtering, rescaling and measurements of 99Tcm-NC uptake were made by a nuclear medicine specialist (RT), who was blinded to the clinical evaluation, laboratory results and MR imaging. The NS measurements of each wrist joint took 10 to 15 min per patient on a workstation. 99Tcm-NC images of all the major joints were acquired in eight-image data collection, thus the total imaging time was about 90 min.








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FIG. 1. 28-yr-old male patient with a disease duration of 5 months. (A) A coloured 99Tcm-NC image of both hands of the patient. The colour scale represents the intensity of the 99Tcm-NC uptake. Arrows point to the areas of measurements. The maximum uptakes in ROI 1, ROI 2, and ROI 3 are 283 counts/pixel, 289 counts/pixel and 177 counts/pixel, respectively. (B) An anatomical illustration of the dominant (left) hand for MRI measurements. The ROIs are drawn based on 99Tcm-NC measurements. (C) Signal intensity (mean pixel value) versus scan acquisition number. Each acquisition consists of 12 continuous slices and is obtained in 69 s with a delay of 1 s between acquisitions. The E-rate in ROI 1 is 1.10 SI/s. (D) The E-rate in ROI 2 is 1.10 SI/s. (E) The E-rate in ROI 3 is 0.43 SI/s. (F) Schematic representation of the signal intensity vs time curves combined from the three ROIs. Note the slower enhancement pattern in ROI 3 compared with the steeper pattern in ROIs 1 and 2.

 
Magnetic resonance imaging
Imaging of the dominant or painful wrist was done using an open-configuration 0.23 T MRI scanner (Philips Medical Systems, MR Technologies Finland, Vantaa, Finland). Dynamic scans were obtained in the coronal plane using a 3D gradient-echo technique. The scans were localized using the initial axial spin-echo localizing sequence. The continuous slices were arranged to cover all carpal bones. The imaging parameters were: TR 30 ms, TE 10 ms, flip angle 40°, matrix size 128 x 256, slice thickness 2 mm, field of view 160 x 160 cm. Each acquisition consisted of 12 slices and was obtained in 69 s. A pre-contrast scan was performed, then a 15 ml Gd-DTPA bolus (Magnevist 469 mg/ml, Schering AG) was injected i.v. through a cannula in the opposite forearm. This injection was given over a period of 15–25 s with a subsequent flush of 10 ml of normal saline, followed by the first post-contrast sequence. Four post-contrast sequences were obtained, each of 69 s duration with a delay of 1 s between them. The imaging time of the dynamic scan was 5 min 50 s. Before contrast-enhanced dynamic imaging, the following sequences were obtained: STIR SE coronal sequence [1800/25/80 ms (TR/TE/TI), 18 x 18 cm field of view, 216 x 256 matrix, one excitation, slice thickness 3 mm, imaging time 9 min 43 s], T2 FSE axial sequence [4000/100 ms (TR/TE), 15 x 15 field of view, 240 x 256 matrix, slice thickness 3 mm, 0.5 mm gap, imaging time 6 min] and T1-weighted 3D GRE coronal sequence [30/10 ms (TR/TE), flip angle 40°, 16 x 16 cm field of view, 256 x 256 matrix, one excitation, slice thickness 2 mm, imaging time 6 min 9 s]. After dynamic imaging, post-contrast coronal T1-weighted 3D GRE images were obtained. Total imaging time was about 40 min.

Assessment of dynamic MRI scans
For the subsequent MRI measurements, a blank anatomical illustration of the carpus with three circular areas (Fig. 1B) was prepared by the nuclear medicine specialist (RT). The three areas were selected based on the quantitative results of NC scanning. The purpose of this selection was to investigate if the nanocolloid uptake values in the different areas within the carpus correlated with the MRI measurements. On MRI image data, ROI circles (5–28 mm2) were placed over the region of maximal synovial enhancement within three pre-selected areas of the carpus. The ROI measurements of the MRI scans were performed by a radiologist (KP) who was blinded to the NC scintigraphy measurements, clinical data and laboratory results. Analysis of the dynamic data was done on a workstation using VIA 2.0 software (Philips Medical Systems, MR Technologies Finland, Vantaa, Finland) and it took about 20 min per patient. Three curves were obtained, plotting the mean pixel intensity of the ROI circle against the time following Gd injection (Fig. 1C–F). In most patients, a rapid steep increase in signal intensity was observed after the first post-contrast sequence at 69 s, followed by a slower increase to the maximum level of enhancement.

For quantitative characterization of these curves, the rate of enhancement (E-rate) per second after the first post-contrast sequence (69 seconds) was calculated as follows:

where SI0 is the signal intensity before the contrast injection and SIt is the signal intensity reached after completing the first post-contrast sequence (69 s).

Evaluation of enhancement after the first post-contrast sequence was chosen, because a previous study revealed significant correlation (Spearman's r>0.60) between the early enhancement rate and the microscopic features of inflammation in the interval of 30 to 120 s after the Gd injection (maximal correlation at 35 to 55 s post-injection) [9]. To compare the results on dynamic MRI and clinical parameters, a single E-rate representing the whole volume of synovial tissue would be needed. However, because it was impossible to measure a single E-rate value from the whole volume of synovial tissue (12 image slices with multiple different sized areas of enhancing tissue at different locations), an average enhancement value from the three previously measured ROIs was calculated.

Scoring of static MRI images
MRI scoring of synovial hypertrophy, bone oedema and bone erosions of the wrist joint was done independently by two observers (KP and JV) by reading the STIR images (bone oedema) and static T1-weighted 3D GRE images obtained before and after contrast enhancement (synovitis and erosions) according to the OMERACT group RAMRIS scoring system [19]. Synovitis was scored on a scale of 0–3 at three different locations: Radioulnar joint, radiocarpal joint and intercarpal–carpometacarpal joints, (total maximum score 9). A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Measurements, in millimetres, of the maximum thickness of enhancing tissue perpendicular to the cortical surface were performed to guide the approximation of the presumed maximum volume of the synovial compartments. Carpal bones, distal radius, distal ulna and bases of metacarpals (15 locations) were scored separately for bone oedema (score 0 to 3 by the volume of oedema: 1, 1–33%; 2, 34–66%; 3, 67–100%) and bone erosions (score 0 to 10, based on the proportion of eroded bone compared with ‘assessed bone volume’: 0, no erosion; 1, 1–10% of the bone eroded; 2, 11–20%, etc.) The maximum score for bone oedema was 45 and that for bone erosions 150. The metacarpophalangeal joints were not evaluated, as they were not completely covered in the image sets.

Statistics
The data were not normally distributed, and correlations between MRI, NC scintigraphy and clinical and laboratory assessments were therefore analysed using Spearman's rank correlation coefficient. Single-measure fixed-effect intraclass correlation coefficients were calculated to investigate the intra-observer reliability of dynamic MRI and quantitative NC scintigraphy measurements. Inter-observer reliability of scoring static MRI scans were calculated with the same method [30]. A level of P<0.05 was considered statistically significant. The SPSS 9.0 was used to conduct analyses.


    Results
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 Abstract
 Introduction
 Material and methods
 Results
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 References
 
The maximum 99Tcm-NC uptake varied from 101 to 560 (mean 223) counts/pixel in three selected areas of the wrists. At the same anatomical locations the MRI E-rate varied from 0 to 2.1 signal intensity units/s (SI/s; mean 0.81). Figure 2 shows the relation between the MRI E-rates and the maximum 99Tcm-NC uptake in the three areas of the wrist. The 99Tcm-NC uptake and MRI E-rates of the three areas varied considerably within the same wrist in most patients: the 99Tcm-NC uptake varied from 9 to 156 (mean 66) counts/pixel and the MRI E-rate from 0.01 to 1.51 SI/s (mean 0.50).



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FIG. 2. Scatterplot with linear regression lines between the MRI synovial enhancement rates and quantitative 99Tcm-NC uptake in three locations in the wrist joints in 20 early RA patients. Spearman's rank correlation coefficients in ROI 1, ROI 2, and ROI 3 are 0.76, 0.88 and 0.95 (P<0.01) respectively.

 
The average 99Tcm-NC uptake in the whole wrist ranged from 97 to 300 (mean 166) counts/pixel. The maximal MRI E-rate measured from the small area of the most intense uptake, the average MRI E-rate, the maximal 99Tcm-NC value and the average 99Tcm-NC uptake of the whole wrist correlated with the MRI score of synovitis and bone oedema, but not with the erosion score, as shown in Table 2. The associations between the laboratory and clinical parameters and imaging results are presented in Table 3. The static MRI scores, maximal and average MRI E-rate, maximal 99Tcm-NC uptake and average 99Tcm-NC uptake of the whole wrist did not correlate with the global disease activity parameters (tender or swollen joint count, HAQ). The ESR correlated with the imaging results. Clinical parameters did not correlate with laboratory parameters. The swollen joint count correlated with the tender joint count (Spearman's r = 0.72, P<0.01).


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TABLE 2. Spearman's correlation coefficients between static semiquantitative MRI scores and quantitative results obtained from dynamic MRI and NC scintigraphy (n = 20)

 

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TABLE 3. Spearman's correlation coefficients between MRI and NC scintigraphy and clinical indicators of inflammation. Consensus reading results for MRI erosion score and bone oedema score

 
The reproducibility of dynamic MRI and NC scintigraphy measurements was tested by remeasurement of 10 randomly picked scans in a blinded fashion. Intra-observer reliability for E-rate and 99Tcm-NC measurements was found to be high, with an intraclass correlation of 0.92; 95% CI 0.84–0.96 and 0.99; 95% CI 0.98–1.00, respectively.

Two readers scored the 28 baseline static MRI wrist scans separately. Inter-observer reliability for the MRI synovitis score was 0.87 (95% CI 0.74–0.94), while the bone oedema score was 0.93 (95% CI 0.85–0.97) and erosion score 0.91 (95% CI 0.82–0.96).

In separate readings, erosions were scored as present in 23 of the 28 MRI scans (82%) by reader 1 and in 20 of the 28 (71%) scans by reader 2. To reach maximum accuracy in scoring erosions and bone oedema, all of the 28 scans were reviewed for a consensus opinion. In the case of the five scans with controversy as to the presence or absence of erosions, the consensus reading showed one scan to reveal an erosion, giving a total of 21 erosive scans (75%). Bone marrow oedema was present according to consensus reading in 17 scans (61%). Synovitis was present according to one or both observers in all scans. The median scores for grading synovitis, bone oedema and erosions are presented in Table 4.


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TABLE 4. Median static MRI scores, (with the range in brackets) of the wrist in 28 early RA patients

 

    Discussion
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
To our knowledge, this is the first paper to explore the value of NC scintigraphy versus contrast-enhanced dynamic MRI in the quantification of synovial membrane inflammation in the wrist joint. NC scintigraphy is commonly used for screening of inflammatory joints based on visual analysis of whole-body scans [23–25]. However, more detailed information about local joint inflammation can be obtained by quantifying the 99Tcm-nanocolloid uptake.

In our study, both quantitative NC scintigraphy and dynamic MRI were found to be feasible methods for detecting the degree of synovial membrane inflammation at the local joint level, even though they require manual processing on a workstation. High correlation between quantitative NC scintigraphy and dynamic MRI indicates a similar diagnostic performance of these imaging methods in detecting synovial inflammation of the wrist. Significant correlations between quantitative results obtained from NC scintigraphy, dynamic MRI and static semiquantitative MRI scores of synovitis and bone oedema further support the concept that these measures are linked to disease activity.

Because 99Tcm-NC image formation is based on the uptake of radiolabelled compound in inflamed tissue, it lacks the spatial resolution and visualization of anatomical structures achieved with MRI. Thus, evaluation of bone oedema and erosions is impossible. Another disadvantage of scintigraphy compared with MRI is the use of a radioactive compound, which exposes patients to small amounts of radiation. However, unlike with MRI, the whole body can be scanned at same time with 99Tcm-NC scintigraphy, and valuable information about possible inflammation in other joints is available. Whole-body 99Tcm-NC scintigraphy could be useful in assessing objectively global disease activity and in guiding clinicians to focus MRI on the most seriously involved joints. At present, analysis of the whole-body 99Tcm-NC scans of the patients is under way, and the results will be published in a forthcoming report.

Dynamic Gd-DTPA-enhanced MRI in quantifying synovial hypertrophy in patients with inflammatory arthritis was first published by Reiser et al. [2]. This group showed a rapid and marked increase of signal intensity in synovial proliferations over time, with a peak value at 56.3 ± 21 s post-injection. Four dynamic MRI studies have included histopathological references [3, 7–9], and only one study has examined the optimal timing of enhancement measurements in correlation with histological inflammatory activity [9]. This study showed the maximum correlation between synovial enhancement and histological inflammatory activity in an arthritic knee joint to occur at 35 to 55 s after the Gd injection, and the correlation continued to be significant until 2 to 2.5 min post-injection. In these studies, the dynamic data were collected from one to four pre-selected image slices. When imaging a wrist joint, the selection of only one slice is problematic because of the more complex anatomy of the wrist compared with the knee joint. In a quantitative assessment of synovial membrane in the wrist joint by Ostergaard et al. [14], the rate of early synovial enhancement could not be measured from a single pre-selected axial image slice in 14 out of 26 wrists. Therefore, despite the disadvantage of a relatively long acquisition time (69 s per sequence), we preferred to select multiple (12) continuous coronal image slices to cover most of the wrist joint volume.

The other approach to quantifying joint synovitis is to measure the synovial tissue volume of the wrist joint [14, 17]. Manual outlining and volume calculation of the enhanced synovial area of the joint is time-consuming, and several semiquantitative scoring methods have been used instead [13, 15]. The OMERACT group released a simple MRI scoring system (RAMRIS) of the wrist and metacarpophalangeal joints, which was validated in an international multicentre trial [20]. Overall the agreement between six groups was satisfactory for measures of synovitis, bone erosions and bone oedema. After practising with wrist MR images of five patients not involved in this study, we decided to employ the RAMRIS score sheet, even though the system is somewhat cruder than some grading systems published previously [13, 15] in terms of its inability to score cartilage thinning or damage and the exclusion of tendonitis and tenosynovitis. Our inter-reader agreement was somewhat better than agreement results published by the OMERACT group. However, we had two readers rather than the six readers of the OMERACT multicentre study, and we performed an inter-reader practice with consensus reading before the reading of the actual study images.

Regional heterogeneity of synovial inflammation in different parts of the arthritic knee joint has been reported previously. In a study by Ostergaard et al. [31], evaluation of the early synovial enhancement rate in small areas of synovial membrane revealed large variation compared with the total synovial membrane enhancement rate of a pre-selected image slice. To investigate this phenomenon and to examine the correlation between quantitative NC scintigraphy and MRI in more detail, three different areas of the wrist were selected for ROI measurements. In our study, similar variation of MRI enhancement rates and radiolabelled nanocolloid uptake were found in different parts of the wrist joint in most patients. The variation between the MRI enhancement rates of the different areas within wrists can be mostly explained by the regional heterogeneity in synovial hypertrophy tissue, but when measuring very small areas of synovial hypertrophy, a partial volume artefact may also have an effect on the measurements. One reason for this regional heterogeneity may be the complex anatomy of the wrist joint, as the joint is composed of several compartments including the first carpometacarpal, common carpometacarpal, intercarpal, radiocarpal and distal radioulnar compartments, which may be differently affected by the disease. In addition to inflammatory activity, the volume of synovial tissue may also contribute to 99Tcm-NC uptake.

To get a single overall measure of the joint inflammation, the average 99Tcm-NC uptake of the whole wrist region was measured. This average measure was used to study the correlation between NC scintigraphy and clinical parameters. However, from multiple wrist MR image slices we were unable to obtain a single enhancement measurement representing the whole volume of inflamed tissue, and we therefore calculated average enhancement values from the three previously selected areas for the comparison of dynamic MRI with clinical parameters, and presented them as average E-rates. The maximal E-rate and the maximal 99Tcm-NC uptake measured in the areas of the most intense enhancement/uptake were also compared with clinical and laboratory results. Measurement of several enhancement curves for average E-rate calculation is time-consuming and similar associations between maximum and average E-rates compared with other study parameters support the idea that a single measurement from the region of the most intense Gd enhancement is sufficient for assessing disease activity.

To determine MRI enhancement rates, implementation of a special rapid gradient-echo sequence, manual placement of ROI circles on the areas of most intense Gd enhancement and calculation of time-dependent enhancement curves by software is required. Obviously, this is more time-consuming than semiquantitative scoring of synovitis by the RAMRIS scoring system from static post-Gd scans. Although dynamic MRI provides more accurate information of the intensity of inflammation at one specific site within the carpus, the significant correlation between MRI E-rate measurements and more easily obtained semiquantitative MRI synovitis score in our study suggests that the RAMRIS system may be adequate in clinical trials and practices, when implementation of dynamic MRI is considered too time-consuming.

Synovitis was present according to one or both observers in all of our patients and bone marrow oedema was present according to consensus reading in 17 of 28 patients (61%). These results are similar compared to those in other papers [15, 37] and indicate a close association between synovitis and bone changes. MRI revealed carpal erosions in 75% of our RA patients who had had symptoms for less than a year (median 5 months). Other MRI studies have also shown that bony erosions develop very early in RA. McQueen et al. [34] reported 45% (19 of 42) of early RA patients to have MRI-detectable erosions at 4 months after the onset of symptoms, the corresponding percentage at 1 yr being 74%. Another study revealed that 18 out of 19 patients with symptoms for less than 1 yr had erosions on MRI of the dominant hand [35]. MRI increases the sensitivity of detecting erosions compared with plain radiography, and there has been some controversy concerning the specificity of erosions detected by MRI. Partial volume artefacts and bone surface irregularity may cause some false-positive findings, but they are mostly avoidable by scoring erosions only if they are present on two different planes (axial and coronal) or in more than one of the adjacent slices of the same sequence. Interestingly, MRI erosions have also been found in normal control subjects and in arthralgia patients [17, 36].

In our study, the MRI and NC scintigraphy parameters correlated with ESR. This may reflect systemic disease activity. A weaker correlation emerged between CRP and the average 99Tcm-NC uptake and between CRP and the wrist MRI synovitis and bone oedema scores. However, no correlation was found between CRP and MRI E-rates. There are conflicting reports concerning MRI and the laboratory parameters of inflammation. In an early RA study of 42 patients, MRI scores of the wrist correlated with CRP and ESR [15]. In some other papers, no correlation was found between the laboratory parameters of inflammation and dynamic MRI [8, 10, 31].

For each patient, NC scintigraphy and MR imaging were performed on the same day to ensure comparable imaging data, but a weakness in our study design was the relatively long time interval between the clinical assessment and imaging. This was due to the limited time capacity of our MRI unit. This may have an effect on non-existent correlation between clinical evaluation (i.e. tender/swollen joint count, HAQ) and imaging results. The involvement of several rheumatologists may also have affected the present results, but this reflects the situation in everyday practice in our institution. In a recent study by Cimmino et al. [33], significant correlations between MRI early enhancement rate and several clinical global disease activity measures (number of swollen and tender joints, the Ritchie Index, Disease Activity Score, HAQ, CRP, ESR, {alpha}2 globulins) were found. On the other hand, some other papers address the discrepancy between clinical evaluation and MRI. Gaffney et al. [8], who studied rheumatoid knee joints, noted no correlation between dynamic MRI and clinical assessment or laboratory parameters. When comparing dynamic MRI of the rheumatoid wrist with clinical parameters, Huang et al. [10] found a weak but significant correlation with the pain score, but not with the other clinical parameters. In a longitudinal study by Jevtic et al. [32], 58% congruence between the clinical and MRI findings was seen. In a 1-yr follow-up study of 34 RA and polyarthritis patients, a decrease in the swollen or tender joint count was detected, but finger synovitis and tenosynovitis on MRI persisted [16]. This may represent the difficulty and low sensitivity of clinical evaluation of disease activity. Nevertheless, the imaging of one joint may not be representative of the global disease activity of a polyarticular systemic disease.

In conclusion, dynamic MRI and quantitative NC scintigraphy show high intermodality correlation in evaluating synovial inflammation of the wrist joint in early RA patients. More detailed and comprehensive information about bone damage is achieved by MRI, but unlike with NC scintigraphy, the evaluation of several joints during the same session is impossible. Both techniques are relatively easy to perform, and they can be used in a long-term follow-up of rheumatoid patients.

The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 

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Submitted 12 March 2004; revised version accepted 8 June 2004.



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