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Musculoskeletal Imaging |
1 From the Departments of Radiology (G.B., M.F.H.S., S.P., W.R.J.), Orthopedics (F.R., A.F., T.S.), and Neurology (K.S.), University Hospital of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Received February 5, 2001; revision requested March 26; revision received August 6; accepted September 28. Address correspondence to G.B. (e-mail: gerd.bodner@uibk.ac.at).
| ABSTRACT |
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MATERIALS AND METHODS: Seventy-nine musculoskeletal tumors (34 malignant, 45 benign) were examined with color and power Doppler US and SWA. Two radiologists independently assessed US images and SWA findings. Echotexture and vessel characteristics such as stenoses, occlusions, loops, shunts, trifurcations, vascular pattern, and resistive index were evaluated. All tumors were subject to US-guided or open biopsy for histologic correlation.
RESULTS: Combined color and power Doppler US and SWA revealed four major (stenosis, occlusion, trifurcation, vascular pattern) and three minor (shunt, self loop, resistive index) vessel characteristics, which proved helpful in differentiating benign from malignant lesions. Echotexture showed moderate sensitivity (82% [28 of 34 tumors]) and low specificity (38% [17 of 45 tumors]). When comparing several combinations of vessel characteristics, a combination of any two major characteristics demonstrated the best results (sensitivity, 94% [33 of 39 tumors]; specificity, 93% [three of 45 tumors]). Combining more than two characteristics resulted in lower sensitivity.
CONCLUSION: Combined color and power Doppler US and SWA may enable assessment of vascular architecture and altered flow of musculoskeletal tumors. Vascular architecture analysis enables differentiation of benign and malignant lesions and evaluation of musculoskeletal tumors.
© RSNA, 2002
Index terms: Muscles, neoplasms Ultrasound (US), Doppler studies, 40.12984, 40.12985 Ultrasound (US), power Doppler studies, 40.12984, 40.12985 Ultrasound (US), tissue characterization, 40.12984, 40.12985
| INTRODUCTION |
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Color Doppler US permits high-spatial-resolution imaging of small vessels (7) and has demonstrated a high capability in depicting and characterizing vascular soft-tissue anomalies (8,9), and power Doppler US accurately depicts tumor vascularity (10). Nevertheless, whether color or power Doppler US or spectral wave analysis (SWA) can enable differentiation between benign and malignant musculoskeletal tumors is not clear (1019).
The purpose of our study was to assess the use of combined color and power Doppler US and SWA in differentiating between malignant and benign musculoskeletal tumors.
| MATERIALS AND METHODS |
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Patients gave written consent for US examination and biopsy. Investigative and interventional procedures were performed on the basis of the guidelines of the Helsinki Declaration (20).
Gray-scale US (HDI 3000 or 5000; Advanced Technology Laboratories, Bothell, Wash) in combination with color and power Doppler US and SWA were prospectively performed by one of two investigators (G.B., M.F.H.S.). The first investigator (G.B.) had more than 6 and the second (M.F.H.S.) more than 2 years of experience in musculoskeletal US. Images from the whole US examination were stored on foil prints and electronically. To determine interobserver agreement, images from gray-scale and color and power Doppler US and SWA in at least five vessels were reviewed by the other investigator, who was blinded to patient data and final histologic diagnosis.
Diagnostic gray-scale US was performed to assess size, location, and internal echotexture of the tumor. At gray-scale US, tumor echotexture was classified as hyperechoic or hypoechoic with reference to surrounding muscle.
The tumor was classified as inhomogeneous or homogeneous. The vascular pattern of each tumor was assessed by using color and power Doppler US. SWA was performed in at least five arterial tumor vessels.
The following color and power Doppler US and SWA criteria were applied:
1. Self or true loop was defined when a self-connective tumor vessel with side branches was visible during color and power Doppler US (21). The loop was scanned in a second plane to confirm the self-vascular connection.
2. Trifurcation was defined when the original vessel was divided into three vessels, with branches originating from the same point (21).
3. Stenosis was diagnosed primarily with color Doppler US while visually searching for aliasing phenomena (22). When a tumor vessel segment demonstrated caliber reduction, as indicated by aliasing phenomena, SWA was performed proximal to, at, and distal to the caliber change. Increase in maximum peak flow velocity in the caliber reduction by more than 100% was considered stenosis (23).
4. An occluded vessel was identified with monophasic waveform and absence of diastolic flow, indicating occlusion in a distal part of the same vessel (23,24).
5. Arteriovenous shunt was diagnosed when a low resistive index (RI) of less than 0.5 was found (9).
6. RI was calculated as maximum systolic velocity - minimum diastolic velocity/maximum systolic velocity. RI was measured in at least five vessels. We determined the ratio of lowest to highest value (RImin/max), where min = minimum and max = maximum.
7. Two vascular patterns were distinguished by using color and power Doppler US: (a) a hierarchic vascular tree, with continuously diminishing vessel size toward the lesion periphery, representing normal vessel architecture (Fig 1); and (b) an anarchic vascular pattern, as described by Less et al (21), consisting of caliber changes, loops, and trifurcations (Fig 2).
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All tumors (n = 79) were subjected to US-guided core-needle biopsy, without any adverse effects. Because of inconclusive biopsy findings, only two patients underwent surgical biopsy. A total of 42 tumors were resected, and further histopathologic evaluation confirmed biopsy findings in all cases; 37 patients did not undergo surgery because of the benign nature of the tumors or the advanced stage of disease.
Histologic examination revealed 34 malignant tumors, including fibrous (n = 3), osseous (n = 3), metastatic (n = 11), vascular (n = 2), lipomatous (n = 5), neural (n = 2), smooth-muscle (n = 5), synovial (n = 2), and unclassified (n = 1) tumors. Forty-five benign tumors included fibrous (n = 13), osseous (n = 4), lipomatous (n = 8), neural (n = 5), vascular (n = 10), and synovial (n = 1) tumors, as well as infectious lesions (n = 4) (Tables 1 and 2). Two intraarticular synovial processes were included in the study, since they arose into the suprapatellar pouch, with extensions in the quadriceps femoris muscle, which made them visible and palpable as tumors of the distal femur. Patients with bone tumors were included in the study because they had a large, dominant, soft-tissue component at presentation. All soft-tissue metastases were true soft-tissue metastases. The patient with tuberculosis and the two patients with abscesses were included, since there were no clinical signs of infection (cold abscesses).
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statistic. Similar to a correlation coefficient,
varies from -1.0 (complete disagreement) to 0 (chance agreement) to +1.0 (perfect agreement). Strength of agreement was labeled as poor (
< 0), slight (
= 00.20), fair (
= 0.210.40), moderate (
= 0.410.60), substantial (
= 0.610.80), or excellent (
= 0.811.00), as suggested in the literature (2528). Whenever ratings differed between observers, the incorrect diagnosis was used for further statistical analysis.
The unpaired t test was performed to compare RIs between benign and malignant musculoskeletal tumors. Distribution of vessel characteristics in benign and malignant musculoskeletal tumors was analyzed with the
2 test for categoric variables. Sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) were calculated for each putative vessel characteristic (absent vs present) with respect to histopathologic diagnosis (29). Sensitivity refers to the probability that color and power Doppler US and SWA reveal malignant tumor when histopathologic findings indicate malignant tumor. PPV refers to the probability of a tumor being malignant when US depicts a malignant tumor. Specificity refers to the probability that US depicts a benign lesion when histopathologic examination shows a benign tumor. NPV refers to the probability of having a benign tumor when US demonstrates a benign lesion.
Vessel characteristics were then evaluated with multivariate analysis by using stepwise logistic regression to identify the set of criteria that would best predict the diagnosis of malignancy. Vessel characteristics representing the best model to indicate malignancy in the multivariate logistic regression analysis were defined as major variables; those not included in the model were defined as minor variables (4,17,18,30).
Sensitivity and specificity of RImin/max were assessed with a receiver operating characteristic curve, which plots sensitivity versus specificity for every possible cutoff point (31). The optimal cutoff ratio, approximately 0.67, was determined visually on the receiver operating characteristic curve. This cutoff value represents the best ratio of minimal and maximal RI for discrimination of benign versus malignant tumors. According to the calculated cutoff value, we divided all tumors into two groups with an RImin/max higher or lower than 0.67 for further categoric testing.
| RESULTS |
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= 0.58) and homogeneity (
= 0.42), good agreement for loops (
= 0.66), shunts (
= 0.78), occlusions (
= 0.78), vascular pattern (
= 0.80), and trifurcations (
= 0.80), and excellent agreement for stenoses (
= 0.85). Evaluation of echotexture provided a sensitivity of 82% (28 of 34 tumors), a PPV of 50% (28 of 56 tumors), a specificity of 38% (29 of 56 tumors), and an NPV of 74% (17 of 23 tumors) for detection of malignancy in musculoskeletal tumors. In contrast, homogeneity had a sensitivity of 85% (29 of 34 tumors), a PPV of 52% (29 of 56 tumors), a specificity of 40% (18 of 45 tumors), and an NPV of 78% (18 of 23 tumors).
The distribution of RI within the tumor tissue, expressed by the ratio of RImin to RImax (RImin/max) for all vessels measured, differed significantly between malignant (mean RImin/max, 0.50 ± 0.19 [SD]) and benign tumors (mean RImin/max, 0.79 ± 0.12; P < .001). Sensitivity, PPV, specificity, and NPV for each vessel characteristic are listed in Table 3. Since all vessel characteristics had a P value less than .05 with the
2 test (Table 3), all were included in subsequent multivariate analysis. Stepwise logistic regression analysis revealed a combination of various vessel characteristics, which included stenoses, occlusions, trifurcations, and anarchic vascular pattern as the best model (P < .001), defining them as major variables, in contrast with shunts, self loops, and RImin/max, which were minor variables. The diagnostic value of different combinations of vessel characteristics such as sensitivity, PPV, specificity, and NPV for any one, two, three, and four of all vessel characteristics can be seen in Table 3. Combinations of major and minor variables were separately tested for sensitivity, PPV, specificity, and NPV, as presented in Table 3. The combinations of any two major characteristics appeared to be the best compromise between sensitivity and specificity. In addition, PPVs and NPVs for these combinations were excellent. In comparison, the combinations of any two minor characteristics or any two random characteristics showed poorer predictive values.
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| DISCUSSION |
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Our study is based on US evaluation of musculoskeletal tumors, since US has excellent spatial resolution, is widely available, and is low in cost. In previous studies (1,3,815), as described earlier, US examination has been limited by the lack of uniform criteria for malignancy. We therefore propose US criteria that may help differentiate between benign and malignant tumors.
Gray-scale US has a high sensitivity for detecting tumors but has not proven useful in differentiating between benign and malignant conditions (13). The contribution of gray-scale US to the final diagnosis in our study was minor. Echotexture and homogeneity can be used to differentiate between a benign or malignant tumor with specificities of 75.6% or 40.0%, respectively.
Unfortunately, when using echotexture and homogeneity to distinguish between benign and malignant tumors, 84.6% and 49.5% of the patients with a diagnosis of malignant tumor had a benign one.
Histologic studies show that the vascular heterogeneity of tumors depends on their degree of malignancy. Progressive growth of malignant tumors requires a newly formed blood supply induced by neoangiogenesis, which primarily starts in venules and subsequently involves the arteries (21,3436). Malignant tumor vessels are histologically characterized by lack of the muscular layer and by irregular contours. They commonly form a heterogeneous reticular network induced by neovascularization. In these chaotic vascular architectures of malignant tumors, occlusions, stenoses, arteriovenous shunts, loops, and trifurcations occur (21). The vascular abnormalities of vessels in malignant tumors result in heterogeneous regional flow patterns (35).
Color and power Doppler US permit detection of vessels as small as 0.2 mm in diameter (7), which is why they are good tools for investigating the vascular architecture of tumors. Several authors (3,8,10,12) have demonstrated the usefulness of color Doppler US for imaging vascular branches in tumors. Accurate visualization of tumor vessels, as permitted by the technical development of color and power Doppler US, has resulted in several attempts to define US criteria for malignancy. Schroeder et al (10) point out that sonomorphologic analysis of tumor vessels appears to be much more reliable than quantitative parameters such as flow velocities or calculated indices. The mean systolic peak flow velocity is said to be higher in malignant tumors, as compared with benign tumors (13,37,38). Paltiel et al (9) and Dubois et al (39) have concluded that high vessel density and high peak arterial Doppler shift can distinguish hemangiomas from other soft-tissue masses. High-frequency Doppler shift in malignant entities has been detected in two studies (11,15). These findings show that color and power Doppler US and SWA can depict vascular irregularities in malignant tumors, whereas the criteria for malignancy, as reported in the literature, vary widely. Other authors (3,14,18,19) controversially discuss or even deny the ability of color and power Doppler US and SWA to enable distinction of benign from malignant lesions.
Our findings show that combined color and power Doppler US and SWA can differentiate between benign and malignant tumors and demonstrate occlusions, stenoses, shunts, trifurcations, and loops. Self loops and trifurcations are detected mainly with power Doppler US, which provides accurate depiction of reticular vessel architecture (Figs 1, 3). In addition, SWA reveals a typical pattern of self loops, characterized by a truncated systolic peak associated with a relatively high diastolic phase (Fig 3b). Corresponding with the visualization of trifurcations and self loops, occlusions, stenoses, and shunts can be primarily demarcated with the help of color and power Doppler US followed with SWA (Fig 4). Consequently, vessel characteristics are verified with color and power Doppler US and SWA so that the origin of signals is reliably identified.
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Combined color Doppler US and SWA permit noninvasive visualization of abnormal vessel architecture, which is commonly found in malignant tumors, as reported in several histologic studies (21,32,40). In agreement with histopathologic findings of malignant and benign tumors, we introduce the concept of major malignancy-related vessel characteristics.
Although this studys findings show the usefulness of color and power Doppler US and SWA in differentiating benign from malignant tumors, some limitations need to be addressed. Malignant tumors less than 1.5 cm in diameter do not induce US-detectable malignant neovascularity (17), which is why these tumors appear nonspecific when using color Doppler US and SWA. Furthermore, completely necrotic tumors also show a lack of vascularization and thus are not accessible for color and power Doppler US.
Biopsy was performed on all musculoskeletal tumors in our series with the help of gray-scale US. Only in two patients were biopsies inconclusive, so that open biopsy was necessary. With reference to the literature (1,2), our score in US-guided core-needle biopsy was excellent.
In conclusion, our study shows that combined color and power Doppler US and SWA permit reproducible visualization of abnormal vascular architecture and enable differentiation between benign and malignant tumors. It enables identification of so-called major and minor vessel characteristics, which are essential for further assessment of tumor vascularization. The best compromise with respect to sensitivity, specificity, PPV, and NPV in differentiating the dignity of musculoskeletal tumors is achieved when combining any two major vessel characteristics. Consequently, combined color and power Doppler US and SWA are most helpful for primary imaging of musculoskeletal tumors.
| FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, G.B., M.F.H.S., K.S.; study concepts, G.B., M.F.H.S., S.P.; study design, G.B., M.F.H.S., K.S., W.R.J.; literature research, G.B., M.F.H.S.; clinical studies, G.B., M.F.H.S., S.P.; data acquisition, G.B., M.F.H.S.; data analysis/interpretation, all authors; statistical analysis, G.B., M.F.H.S., K.S.; manuscript preparation, G.B., M.F.H.S., S.P., K.S., W.R.J.; manuscript definition of intellectual content, G.B., M.F.H.S., A.F., W.R.J.; manuscript editing and revision/review, G.B., M.F.H.S., S.P., W.R.J.; manuscript final version approval, G.B., M.F.H.S., W.R.J.
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