To relate histologic changes in rotator cuff tendons to the appearance on T1-weighted as well as fat-suppressed T2-weighted and proton density-weighted magnetic resonance imaging (MRI) sequences.
To relate histologic changes in rotator cuff tendons to the appearance on T1-weighted as well as fat-suppressed T2-weighted and proton density-weighted magnetic resonance imaging (MRI) sequences.
T1-weighted, fat-suppressed T2-weighted and fat-suppressed proton density-weighted sequences of 18 cadaveric shoulders were acquired. The supraspinatus, infraspinatus, and subscapularis tendons were evaluated histologically. Twenty-six abnormalities were found in 23 of 37 tendons. In addition, histologically normal tendon parts (n = 32), including three segments with normal histology but abnormal MR signal, considered to represent magic angle effects, were defined. All regions of interest (ROIs) were evaluated by two musculoskeletal radiologists independently and blinded to histology.
In the 26 areas with anatomically intact tendons but abnormal histological findings mucoid degeneration (n = 13), chondroid metaplasia (n = 11), fatty infiltration (n = 1), and foreign-body granuloma (n = 1) after tendon suture were found. Compared to normal tendon, mucoid degeneration was hyperintense on T2-weighted fat-suppressed (P = 0.007) and on proton density-weighted fat-suppressed images (P = 0.006). Chondroid metaplasia was hyperintense compared to normal tendon in all sequences (P < 0.05). Mucoid degeneration was hypointense compared to chondroid metaplasia on T2-weighted fat-suppressed images (P = 0.038) and hypointense compared to magic angle artifacts on T1-weighted images (P = 0.046).
Chondroid metaplasia of rotator cuff tendons appears to be more common than expected. Both mucoid degeneration and chondroid metaplasia may explain increased tendon signal on MR images of the rotator cuff. J. Magn. Reson. Imaging 2010;32:165–172. © 2010 Wiley-Liss, Inc.
MAGNETIC RESONANCE IMAGING (MRI) signal abnormalities of rotator cuff tendons are common. They may be caused by a number of structural changes but also by artifacts. There are few articles comparing histological findings with signal alterations (1–4). Gagey et al (1) evaluated the histology of macroscopically normal supraspinatus tendons of young (14–28 years old) asymptomatic individuals and described fibrillary degeneration, fibrous dystrophy, and eosinophilic transformation of tendon collagen as early degeneration. Kjellin et al (3) reported that areas with increased signal intensity seen on proton density (PD)-weighted images (without further increased signal intensity on T2-weighted images) and an indistinct margin at the articular side of the tendon correspond to eosinophilic, fibrillary, and mucoid degeneration as well as scarring. Increased signal persisting on T2-weighted images was associated with severe degeneration and tendon fiber disruption.
To our knowledge, currently published histological investigations have been limited to the supraspinatus tendon and limited numbers of sequences (PD-weighted and T2-weighted sequences). Thus, the purpose of our study was to relate histologic changes in rotator cuff tendons to their appearance in T1-weighted as well as fat-suppressed T2-weighted and proton density-weighted MR sequences.
The specimens were obtained from autopsies. At the involved institution the permission to perform autopsies includes the use of body parts for research purposes. Such permission was obtained from relatives.
Eighteen unembalmed cadaveric shoulder specimens were harvested and deep-frozen at −40°C immediately after death. Due to legal reasons, no information regarding the identity, gender, age, or medical history of the donors was available. After MRI, the infraspinatus, supraspinatus, and subscapularis tendons including their bony attachment to the humerus were removed and evaluated macroscopically and histologically. Because the specimens were used for an orthopedic shoulder surgery course before harvesting, some tendons were lost for histological evaluations. Fourteen supraspinatus, 17 infraspinatus, and six subscapularis tendons were evaluated histologically.
All specimens were allowed to thaw for 24 hours at room temperature prior to MRI. A 1.5-T system (Avanto, Siemens Medical Solutions, Erlangen, Germany) was employed. A four-element shoulder array coil was used. The specimen was placed in the coil similar to the shoulder of a supine patient to achieve a normal anatomic orientation of the tendons to the main magnetic field.
T1-weighted (T1w) spin-echo sequences (repetition time [TR], 539 msec; echo time [TE], 15 msec; field of view [FOV], 14 × 14 cm; section thickness, 3 mm; matrix size, 512 × 512; number of excitations [NEX], 2; bandwidth [BW], ± 31 kHz), fat-suppressed T2-weighted (T2wfs) fast spin-echo sequences (TR, 3040 msec; TE, 71 msec; FOV, 14 × 14 cm; section thickness, 3 mm; matrix, 512 × 512; NEX, 1; echo train length [ETL], 7; BW, ± 31 kHz), and fat-suppressed proton density-weighted (PDwfs) fast spin-echo sequences (TR, 2640 msec; TE, 15 msec; FOV, 14 × 14 cm; section thickness, 3 mm; matrix, 512 × 512; NEX, 2; ETL, 7; BW, ± 28 kHz) were acquired in the transverse, angled sagittal (parallel to the glenoid joint surface), and angled coronal (perpendicular to the glenoid joint surface) planes. All images were stored and evaluated on a PACS.
The removal of the tendons was performed by an orthopedic surgeon with specialization in shoulder orthopedics. During this procedure the tendons were evaluated macroscopically by the orthopedic surgeon and a musculoskeletal radiologist in consensus.
In case of partial or complete tendon tears, the size and location with respect to the bony insertion of the tendons were noted.
Immediately after removal and macroscopic evaluation the tendons were placed in buffered 10% formalin and stored in a refrigerator at 5°C. For staining the specimens were washed in tap water and dehydrated using four alcoholic solutions with increasing concentration.
The tendons were embedded in paraffin and cut longitudinally in 2–4-μm sections through the middle of the tendon using a precision saw (Leica SP 1600; Leica Instruments, Nussloch, Germany) and stained with hematoxylin and eosin (H&E).
Histological evaluation was then performed by a musculoskeletal pathologist with 8 years of experience. Evaluation was performed using a high-quality light microscope (Olympus BX41, Center Valley, PA). Mucoid degeneration was diagnosed in the presence of plump tenocytes with chondroid appearance, and discontinuous, disorganized collagen fibers with or without mucoid ground substance. Fatty infiltration was defined as fat tissue between otherwise normal tendon fibers. Lipoid degeneration was defined as fat tissue between degenerated and fragmented tendon fibers. Chondroid metaplasia was defined as fibrous cartilage without communication to the fibrous cartilage that is normally found at the tendon insertions.
The involved pathologist found 26 locations with pathological changes and determined a region of interest (ROI) for each location: eight ROI in seven different supraspinatus tendons, 17 ROI in 14 different infraspinatus tendons, and one ROI in one subscapularis tendon. In addition, 32 ROIs with histologically normal tendon (Fig. 1) substance were determined, three of which were placed in regions with increased MR signal seen in at least one sequence and assumed to represent magic angle effects due to the orientation of the tendon fibers with respect to the main magnetic field, B0. The distance of each ROI from the bony attachment of the tendon was measured using a light microscope (Leica M420, Leica-Microsystems, Glattbrugg, Switzerland) and an attached digital camera (Leica DFC320, Leica-Microsystems). Length was measured digitally using a dedicated software (IM1000, Leica-Microsystems).
To prevent interaction of tendon tears with histological and radiological readout, all ROIs with normal histology were determined at least 5 mm distant to any abnormality seen on histological images. The location of the ROI with pathologic changes was compared to the location of the tendon tears of macroscopic evaluation. All ROI with pathologic changes were at least 5 mm distant to tendon tears.
To identify the correct location of the histologically defined ROI in MR images, the measurements from the bony attachment of the tendon to the ROI were used. A curved line through the middle of the tendon beginning at the most proximal end of the tendon insertion was plotted using a DICOM viewing software (OsiriX, v. 3.2.1, OsiriX Foundation, Geneva, Switzerland). Then a circular ROI with a diameter of 3 mm was placed at the site corresponding to the histological abnormalities.
Two musculoskeletal radiologists with 20 and 10 years of experience analyzed all previously defined ROI independently and blinded to the results of histology. Signal intensity inside the ROI was graded using the signal intensity of bone, fat, muscle, and joint fluid as the reference (Table 1).
|0||Hypointense as cortical bone|
|1||Between cortical bone and deltoid muscle|
|2||Isointense compared to deltoid muscle|
|3||Between deltoid muscle and subcutaneous fat||Between deltoid muscle and joint fluid|
|4||Brighter than (subcutaneous) fat||Brighter than joint fluid|
Weighted kappa values were calculated in order to describe interreader agreement. MR grading of signal intensity and involved area of tendon diameter of the different types of degeneration were compared using a Wilcoxon signed rank test. SPSS (v. 16.0 mac; Chicago, IL) software was used for statistical analysis.
Thirty-seven tendons were evaluated (14 supraspinatus / 17 infraspinatus / 6 subscapularis). Macroscopically there were five partial tendon tears (1/2/2). Five tendons had a transmural tear (4/1/0).
Histologically, mucoid degeneration (Fig. 2) was found in 13 tendons (two supraspinatus, 11 infraspinatus, 0 subscapularis). Eleven tendons (five supraspinatus, five infraspinatus, one subscapularis) had chondroid metaplasia (Figs. 3, 4), and one (supraspinatus) had fatty infiltration (Fig. 5). Mucoid degeneration and chondroid metaplasia were found simultaneously in three infraspinatus tendons. Chondroid metaplasia was never found at the same location as mucoid degeneration but was found directly distal (closer to the tendon insertion) to the location of mucoid degeneration. In one specimen there was a foreign body granuloma with a piece of suture material from previous rotator cuff repair.
Interreader agreement with regard to signal intensity was moderate in T1w (κ 0.56), almost perfect in T2wfs (κ 0.84), and substantial in PDwfs images (κ 0.75). Evaluation based on T1w (κ 0.24) and PDwfs (κ −0.07) images were not successful. The results of the MR evaluation of the different ROIs, separate for the different histologic changes, are presented in Table 2.
|Histologic or morphologic change||Signal intensity||Involved tendon thickness|
|Median (Range)||Median (Range)|
|Normal tendon (without magic angle)||T1w||2 (1-3)||2 (1-2)||4 (2-4)||3 (1-4)|
|T2wfs||1 (0-3)||1 (0-3)||3 (1-4)||3 (1-4)|
|PDwfs||1 (0-2)||1 (0-3)||4 (1-4)||3 (1-4)|
|Mucoid degeneration||T1w||1 (1-2)||2 (1-2)||4 (4-4)||4 (2-4)|
|T2wfs||1 (0-3)||2 (0-4)||4 (1-4)||3 (1-4)|
|PDwfs||2 (1-3)||2 (1-4)||4 (2-4)||3 (2-4)|
|Chondroid metaplasia||T1w||2 (1-3)||2 (1-3)||4 (2-4)||3 (2-4)|
|T2wfs||2 (1-3)||2 (1-3)||3 (1-4)||3 (1-4)|
|PDwfs||2 (1-3)||2 (1-3)||4 (2-4)||3 (2-4)|
|Fatty infiltration||T1w||4 (4-4)||4 (4-4)||4 (4-4)||4 (4-4)|
|T2wfs||3 (3-3)||3 (3-3)||4 (4-4)||4 (4-4)|
|PDwfs||3 (3-3)||3 (3-3)||4 (4-4)||4 (4-4)|
|Magic angle artifact||T1w||2 (1-2)||2 (2-2)||4 (4-4)||4 (3-4)|
|T2wfs||2 (2-2)||2 (1-2)||2 (2-3)||4 (3-4)|
|PDwfs||2 (2-2)||2 (1-2)||3 (2-4)||4 (4-4)|
Compared to normal tendon, mucoid degeneration was characterized by significantly (Wilcoxon signed rank test, P < 0.05) increased signal on T2wfs (P = 0.007) and PDwfs (P = 0.006) images (Table 3). Mucoid degeneration was slightly hypointense compared to magic angle artifacts on T1w images (P = 0.046), and hypointense compared to chondroid metaplasia on T2wfs images (P = 0.038). The significant differences in signal intensities of the different histologic changes are demonstrated in Table 3.
|Intensity in T1-weighted sequence|
|Chondroid metaplasia > Normal tendon||0.029|
|Magic angle artifact > Mucoid degeneration||0.046|
|Intensity in T2-weighted fat-suppressed sequence|
|Chondroid metaplasia > Normal tendon||< 0.001|
|Chondroid metaplasia > Magic angle artifact||< 0.001|
|Chondroid metaplasia > Mucoid degeneration||0.038|
|Mucoid degeneration > Normal tendon||0.007|
|Intensity Proton density-weighted fat-suppressed sequence|
|Chondroid metaplasia > Normal tendon||0.001|
|Mucoid degeneration > Normal tendon||0.006|
There was vast overlap concerning the spectrum of signal intensity of the different histological patterns (Fig. 6 6). In ROIs with normal tendon histology (n = 29), signal intensity was ≥3 in three ROIs (10%) on T1w images, in four ROIs (14%) on T2wfs images, and in two ROIs (7%) on PDwfs images. The signal intensity of mucoid degeneration (n = 13) was <3 in 13 ROIs (100%) on T1w images, in 10 ROIs (77%) on T2wfs images, and in 10 ROIs (77%) on PDwfs images. In ROIs with chondroid metaplasia (n = 11), signal intensity was <3 in 10 ROIs (91%) on T1w images, in eight ROIs (73%) on T2wfs images, and in seven ROIs (64%) on PDwfs images.
Accordingly, a signal intensity grade 1 or 2 in an ROI on T1w/T2wfs/PDwfs images had a sensitivity of 90%/86%/93% and a specificity of 4%/25%/29% for normal tendon substance. Conversely, a signal intensity grade 3 or 4 in an ROI on T1w/T2wfs/PDwfs images had a sensitivity of 4%/25%/29% and a specificity of 90%/86%/93% for tendon pathology.
A number of structural changes can alter MR signal of rotator cuff tendons. Normal tendons are characterized by hypointensity in T1w, T2wfs, and PDwfs MR images. T1w sequences can be applied to identify tendinopathy before tendon tears arise. Compared to normal tendon, tendinopathic tendon segments are typically diffusely hyperintense in T1w images. Unless there is a partial tendon tear, these segments do not show any signal abnormality in T2-weighted images (3).
In our study population, mucoid degeneration was the most common abnormality. This finding is in accordance with prior publications (1–5). Rather unexpectedly, the second most common finding was chondroid metaplasia. Chondroid metaplasia has been described in the tibialis posterior tendon (6, 7). There are only few publications that mention chondroid metaplasia in rotator cuff tendons (8–10). Hashimoto et al (9) reported a frequency of 21% for chondroid metaplasia in supraspinatus tendons. In our specimens, chondroid metaplasia was found in 42% of supraspinatus tendons, 23% of infraspinatus tendons, and 17% of subscapularis tendons. The importance of these lesions is largely unknown. Longo et al (11) suggested that they were potential precursors of a tendon tear. Matthews et al (10) evaluated tears in supraspinatus tendons and found chondroid metaplasia and amyloid deposition more often in large tears. They described an inverse proportional relationship between histological changes indicative of repair and inflammation, such as increased fibroblast cellularity, intimal hyperplasia, increased expression of leukocyte and vascular markers, and the size of the tear. However, it remains unclear if chondroid metaplasia favors the development and enlargement of rotator cuff tears or denotes a reactive change caused by rotator cuff tears. In our specimen, all ROIs with chondroid metaplasia and mucoid degeneration were at a distance of at least 5 mm from any rotator cuff tears. Compared to mucoid degeneration, chondroid metaplasia seems to arise more distally (closer to the insertion) in the tendon. However, because we had only three tendons with both degeneration patterns, this could have happened coincidentally. Altogether, we wonder if mucoid degeneration and chondroid metaplasia really are two different entities, or just two different stages (variants) of the same pathologic process. It could be possible that tendon degeneration starts with a cellular reaction of the tenocytes. In this case the tenocytes could transform to fibroblasts and either start producing a scar or undergo chondroid metaplasia, resulting in production of extracellular matrix. Subsequently, chondroid metaplasia degeneration could occur with resultant cell loss from necrosis and transformation to mucoid degeneration. However, we have no proof of this.
Due to the vast overlap concerning the spectrum of signal intensity of the different histological patterns, signal intensities of grade 3 or 4 are not an appropriate criteria to diagnose tendon derangements. Conversely, signal intensities of grade 1 or 2 do not imply normal tendon histology. Thus, we were unable to stratify normal tendon, mucoid degeneration, and chondroid metaplasia based on differences in signal intensity.
The single area of fatty infiltration was hyperintense on T1w images, as expected, and may mimic mucoid degeneration. Unexpectedly, however, this abnormality was also hyperintense on fat-suppressed images. The histological slides of this lesion were reviewed and a localized, diffuse edema between the fat cells was found. The pathogenesis of this edema remains unknown. However, the most likely explanation was an artifact due to freezing and thawing of the specimen. This situation may not be reproducible in vivo. To the best of our knowledge, there is no publication dealing with the influence of freezing and thawing of the specimen on the signal intensity of the tissues. Based on the low cellularity and metabolic activity of tendons, however, the influence of specimen handling on MR characteristics can be expected to be low when compared to other types of tissue.
The prevalence of fatty infiltration and its influence on mechanical properties of tendons are not known.
Signal intensity may also be increased in normal tendons. Magic angle artifacts have been described for short-TE sequences (4, 12, 13). They are most pronounced where the angle between tendon fibers and the B0 magnetic field is 54.7° (14–16). In addition, interdigitation effects have been described at the musculotendinous junction in the supra- and infraspinatus tendons for short-TE sequences (4, 12, 13). One potential explanation for this increased signal is the variable morphology of the musculoskeletal junction and partial volume effects of muscle and tendon tissues. The signal changes are most pronounced when the shoulder is internally rotated (5). Based on a cadaveric study with MR-histological correlation Kjellin et al (3) stated that areas with high signal intensity on proton density-weighted images and normal signal on T2-weighted (T2w) images with blurred borders related to mucoid degeneration. Conversely, high signal on T2w images most probably indicated severe degeneration and substance defects. If signal intensity on T2-weighted images is higher than adjacent muscle tissue it is more likely to be a tear than a magic angle artifact (17). Our results indicate that similar rules are valid for the more commonly used fat-suppressed spin-echo sequences.
Interreader agreement was best for T2wfs and PDwfs images. In the evaluation of the extent of involved tendon thickness T2wfs images were superior to T1w or PDwfs images.
Study limitations relate to the relatively small number of specimen, which precluded use of a more detailed grading scale for signal intensities. Small differences with regard to sequences and the various types of tendon abnormalities may be underestimated using a grading scale with only four signal intensity grades. The lack of information about age, gender, or medical history of the donors limits the ability to define the symptomatic or asymptomatic aspect of the tendon.
In conclusion, chondroid metaplasia of rotator cuff tendons appears to be more common than expected. Both mucoid degeneration and chondroid metaplasia may explain increased tendon signal on MR images of the rotator cuff.