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Validity of the minimal resistance index for discrimination between benign and malignant breast tumours
European Journal of Ultrasound 7 (1998) 189 – 193
Clinical report
Validity of the minimal resistance index for discrimination between benign and malignant breast tumours Carlos Villena-Heinsen a,*, Jochem Ko¨nig b, Bernd von Tongelen a, A. Kubilay Ertan a, Martin Holla¨nder a, Isaak Tossounidis a, Werner Schmidt a a
Department of Gynaecology and Obstetrics, The Uni6ersity Hospital Homburg/Saar, 66421 Homburg/Saar, Germany b Institute of Medical Biometrics, Epidemiology and Computer Science, The Uni6ersity Hospital Homburg/Saar, 66421 Homburg/Saar, Germany Received 24 July 1996; received in revised form 30 May 1997; accepted 22 December 1997
Abstract We investigated the validity of the flow parameter minimal resistance index (min RI) for discrimination of breast tumours. Colour and spectral Doppler sonography was performed on 114 patients. An increase in number of tumour vessels was paralleled by a significant drop of the minimal (min) RI (p=0.004) and increase of the maximal (max) RI (p=0.03) while mean RI was not influenced. The present results question the validity of min RI as parameter for discrimination of breast tumours. Min RI does not represent the actual flow resistance. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Breast tumour; Breast sonography; Doppler blood flow; Tumour vascularisation; Resistance index (RI); Ultrasound
1. Introduction Investigators commonly used several indices based on vessel resistance (Campbell et al., 1992; Kawai et al., 1992; Kurjak et al., 1990), absolute
* Corresponding author. Tel.: + 49 6841 168122; + 49 6841 168122.
velocity (Madjar et al., 1994; Minasian and Bamber, 1982) and number of tumour vessels (Cosgrove et al., 1993; Madjar et al., 1994; McNicholas et al., 1993) to differentiate malignant from benign tumours using colour Doppler sonography. Following the hypothesis that malignancy correlates with a lower flow resistance most of the investigators classified the tumours according to the min RI (or minimal pulsatility index).
0929-8266/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0929-8266(98)00031-7
190
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193
In this study we investigated the relation between the number of recorded tumour vessels and the calculation of minimal (min), maximal (max) and mean resistance index (RI).
2. Patients and methods We prospectively studied 114 successive patients with unilateral and unicentric sonographically demonstrable breast lump who underwent surgical excision. After conventional B-mode sonography, colour Doppler sonography was performed. Tumour and both breasts, each divided into four quadrants were investigated. In the tumour area all detectable flow signals were investigated by spectral analysis. In each quadrant—for reasons of time — we investigated maximally two vessels. Flow signals mandatory had a distance larger than 2 cm from the tumour border in order to be considered for evaluation in a quadrant. The healthy breast tissue was evaluated in two different manners: based on min, mean and max RI calculated for each quadrant an average value was calculated for min, mean and max RI for all eight quadrants. Alternatively the min and max RI were determined from all 8 to 16 calculated RI’s and only the mean RI was calculated (RI = systolic velocity – diastolic velocity – systolic velocity). Acuson sonography equipment was used (Mountain View, CA), model 128 XP 10. We used a 7 MHz linear transducer. In the colour Doppler mode the transducer automatically switches over to 5 MHz. Colour Doppler tuning was aimed at optimizing registration of low velocity flow and weak colour signals. Statistical analysis of tumor and other regions was done by two- tailed t-test for dependent samples.
3. Results Histology of the 114 biopsies showed 63 carcinomas and 51 benign tumours. Mean age was 55 years (21 – 84 years); 59 patients were premenopausal, 55 postmenopausal. In all 114 tumours on average 3.391.6 S.D. (1 – 9) vessel
cross sections were recorded and investigated by spectral analysis. In each quadrant one or two vessels (on average 1.59 0.5 S.D.) were investigated. In cases of diastolic zero flow (three measurements) and of missing flow in the quadrants (1.8%) no RI was calculated. Carcinomas had significantly more tumour vessels (between 1 and 9, on average 3.69 0.2 S.D.) than benign tumours (between 1 and 6, on average 2.89 0.2 S.D.), p= 0.008. An larger number of investigated tumour vessels was associated to a significantly lower min RI (p= 0.004) and a significantly higher max RI (p= 0.08), while mean RI did not change (p= 0.58). Fig. 1 shows the difference between tumour area and the average value of the eight healthy quadrants for min RI (left), mean RI (center) and max RI (right), according to number of tumour vessels investigated. With increasing number of tumour vessels investigated, there was a higher max RI and a lower min RI in the tumour. As shown in Table 1, the average min RI from all tumours (based on average 3.3 measurements) was 0.629 0.11 S.D. This was significantly lower, than the average min RI from the eight healthy quadrants (0.659 0.08 S.D.) that based on the average of eight quadrants with 1.5 measurements each (p= 0.0001). But if all the measured min RI of the eight quadrants (on average 12 measurements) were taken into account the min RI was 0.549 0.1 S.D. and significantly lower than in the tumour (pB 0.0001). For max RI exactly the opposite correlations were observed. Mean RI was the only parameter showing independency of the number of investigated vessels. The relation of vessel number to RI was corroborated by the same analysis done in those 51 patients which had only one or two tumour vessels as well as by analyzing the RI (min, max, mean) from the first two vessels of the 114 investigated tumours. As shown in Table 1, the min RI did not differ significantly between tumour and healthy breast tissue when the calculation was based on the average of eight quadrants but was significantly higher if the calculation included all measurements within eight quadrants (pB 0.00001).
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193
191
Fig. 1. Differences between RI from tumour area and mean of the eight healthy quadrants (positive difference above, negative difference below zero line) for the parameters min RI (left), mean RI (middle) and max RI (right column) with differentiation for number of vessel cross sections in the tumour area on the abscissa.
4. Discussion Differences in the number of vessels detected may be influenced by several factors as: the impossibility to determine the exact number of vessels using a 2-dimensional assessment, the duration of the examination, the technology used and the experience of the examinator. Taking into consideration our aim to investigate all detectable tumour blood flow, supported by the considerable duration of each examination, we expected a correlation between the number of cross sections detected and the real number of existing vessels.
Irrespective of menopausal state and of the differentiation benign–malignant tumours an increasing number of tumour vessel cross sections correlated with decreasing min RI (p= 0.004), increasing max RI (p= 0.03) and stable mean RI. Paradoxically we observed in the tumour at the same time the lowest (min) RI and the highest (max) RI compared to the average from the eight healthy quadrants. As an increase in perfusion— represented by an increased number of vessels— should be associated with a decreased flow resistance, a general decrease of the min, max and mean RI was to be expected. Lack of uniformity of the results of these three
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193
192
Table 1 Average values and statistical analysis for min, max and mean RI in tumour, average of eight quadrants and complete number of measurements
Mean number of vessels min RI (n= 114) mean RI (n = 114) max RI (n = 114)
Mean number of vessels min RI (n =51)
Mean number of vessels min RI (n = 114)
Average of eight quadrants
Tumour
All measurements within eight quadrants
1.5
3.3
12
0.65 (9 0.08) p= 0.0001 0.68 (9 0.07) p= 0.13 0.70 (9 0.07) pB0.0001
0.62 (90.11) pB0.0001 0.69 (9 0.09) 0.75 (9 0.1) pB0.0001
Average of eight quadrants
Tumour with one or two vessels
All measurements within eight quadrants
1.5
1.6
12
0.66 (9 0.8) p= 0.67
0.65 (90.11) pB0.00001
Average of eight quadrants
Tumour, first two detected vessels
All measurements within eight quadrants
1.5
2.0
12
0.65 (9 0.01) p= 0.63
0.64 (9 0.01) pB0.00001
resistance indices, however, pointed towards a significant influence of vessel number on min RI and max RI. Therefore, these two indices were not the result of the real flow resistance but of mathematical minimizing and maximizing operations. Final proof for the existence of a minimizing–maximizing effect was gained by comparing the different number of measurements in tumour and healthy breast tissue. The results of this study pointed towards the existence of a purely mathematical minimizing effect, which implicitly influences min RI and max RI. The probability to detect a low min RI is strongly influenced by the number of vessel cross sections. So it is not surprising that most published studies about differentiation between benign and malignant tumours (including gynaecological tumours) have found significantly lower min RI in the on average better perfused malignant tumours (Campbell et al., 1992; Kawai et al., 1992; Kurjak et al., 1990; Sohn et al., 1992). The present study questions the validity of min RI for the registration of true flow resistance and as parameter for discrimination
0.54 (9 0.1) 0.68 ( 90.07) 0.80 ( 90.07)
0.55 (9 0.01)
0.54 ( 9 0.01)
between benign and malignant tumours.
References Campbell, S., Bourne, T.H., Reynolds, K., Hampson, J., Royston, P., Whithehead, M.I., Collins, W.P. Role of colour Doppler in an ultrasound-based screening programme. In: Sharp, F., Mason, W.P., Creasman, W., editors. Ovarian Cancer 2: Biology, Diagnosis and Management. London: Chapman and Hall, 1992:237– 247. Cosgrove DO, Kedar RP, Bamber JC, Al-Murrani B, Davey JBN, Fischer C, McKinna JA, Svensson WE, Tohno E, Vagios E, Alsanjari NA. Breast diseases: colour Doppler US in differential diagnosis. Radiology 1993;189:99 –104. Kawai M, Kano T, Kikkawa F, Maeda O, Oguchi H, Tomoda Y. Transvaginal Doppler ultrasound with colour flow imaging in the diagnosis of ovarian cancer. Obstet Gynecol 1992;79:163 – 7. Kurjak A, Jurkovic D, Alfirevic Z, Zalud I. Transvaginal colour Doppler imaging. J Clin Ultrasound 1990;18:227– 31. Madjar H, Pro¨mpeler H, Sauerbrei W, Wolfahrt R, Pfleiderer A. Color Doppler flow criteria of breast lesions. Ultrasound Med Biol 1994;20:849 – 58. McNicholas MM, Mercer PM, Miller JC, McDermott EW, O’Higgins NJ, MacEarlean DP. Colour Doppler sonography in the evaluation of palpable breast masses. Am J
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193 Roentgenol 1993;161:765–71. Minasian H, Bamber JC. A preliminary assessment of an ultrasonic doppler method for the study of blood flow in human breast cancer. Ultrasound Med Biol 1982;8:357 – 64.
.
193
Sohn Ch, Grischke EM, Wallwiener D, Kaufmann M, Fournier D, von Bastert G. Die sonographische Durchblutungsdiagnostik gut- und bo¨sartiger Brusttumoren. Geburtsh u Frauenheilk 1992;52:397 – 403.
Clinical report
Validity of the minimal resistance index for discrimination between benign and malignant breast tumours Carlos Villena-Heinsen a,*, Jochem Ko¨nig b, Bernd von Tongelen a, A. Kubilay Ertan a, Martin Holla¨nder a, Isaak Tossounidis a, Werner Schmidt a a
Department of Gynaecology and Obstetrics, The Uni6ersity Hospital Homburg/Saar, 66421 Homburg/Saar, Germany b Institute of Medical Biometrics, Epidemiology and Computer Science, The Uni6ersity Hospital Homburg/Saar, 66421 Homburg/Saar, Germany Received 24 July 1996; received in revised form 30 May 1997; accepted 22 December 1997
Abstract We investigated the validity of the flow parameter minimal resistance index (min RI) for discrimination of breast tumours. Colour and spectral Doppler sonography was performed on 114 patients. An increase in number of tumour vessels was paralleled by a significant drop of the minimal (min) RI (p=0.004) and increase of the maximal (max) RI (p=0.03) while mean RI was not influenced. The present results question the validity of min RI as parameter for discrimination of breast tumours. Min RI does not represent the actual flow resistance. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Breast tumour; Breast sonography; Doppler blood flow; Tumour vascularisation; Resistance index (RI); Ultrasound
1. Introduction Investigators commonly used several indices based on vessel resistance (Campbell et al., 1992; Kawai et al., 1992; Kurjak et al., 1990), absolute
* Corresponding author. Tel.: + 49 6841 168122; + 49 6841 168122.
velocity (Madjar et al., 1994; Minasian and Bamber, 1982) and number of tumour vessels (Cosgrove et al., 1993; Madjar et al., 1994; McNicholas et al., 1993) to differentiate malignant from benign tumours using colour Doppler sonography. Following the hypothesis that malignancy correlates with a lower flow resistance most of the investigators classified the tumours according to the min RI (or minimal pulsatility index).
0929-8266/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0929-8266(98)00031-7
190
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193
In this study we investigated the relation between the number of recorded tumour vessels and the calculation of minimal (min), maximal (max) and mean resistance index (RI).
2. Patients and methods We prospectively studied 114 successive patients with unilateral and unicentric sonographically demonstrable breast lump who underwent surgical excision. After conventional B-mode sonography, colour Doppler sonography was performed. Tumour and both breasts, each divided into four quadrants were investigated. In the tumour area all detectable flow signals were investigated by spectral analysis. In each quadrant—for reasons of time — we investigated maximally two vessels. Flow signals mandatory had a distance larger than 2 cm from the tumour border in order to be considered for evaluation in a quadrant. The healthy breast tissue was evaluated in two different manners: based on min, mean and max RI calculated for each quadrant an average value was calculated for min, mean and max RI for all eight quadrants. Alternatively the min and max RI were determined from all 8 to 16 calculated RI’s and only the mean RI was calculated (RI = systolic velocity – diastolic velocity – systolic velocity). Acuson sonography equipment was used (Mountain View, CA), model 128 XP 10. We used a 7 MHz linear transducer. In the colour Doppler mode the transducer automatically switches over to 5 MHz. Colour Doppler tuning was aimed at optimizing registration of low velocity flow and weak colour signals. Statistical analysis of tumor and other regions was done by two- tailed t-test for dependent samples.
3. Results Histology of the 114 biopsies showed 63 carcinomas and 51 benign tumours. Mean age was 55 years (21 – 84 years); 59 patients were premenopausal, 55 postmenopausal. In all 114 tumours on average 3.391.6 S.D. (1 – 9) vessel
cross sections were recorded and investigated by spectral analysis. In each quadrant one or two vessels (on average 1.59 0.5 S.D.) were investigated. In cases of diastolic zero flow (three measurements) and of missing flow in the quadrants (1.8%) no RI was calculated. Carcinomas had significantly more tumour vessels (between 1 and 9, on average 3.69 0.2 S.D.) than benign tumours (between 1 and 6, on average 2.89 0.2 S.D.), p= 0.008. An larger number of investigated tumour vessels was associated to a significantly lower min RI (p= 0.004) and a significantly higher max RI (p= 0.08), while mean RI did not change (p= 0.58). Fig. 1 shows the difference between tumour area and the average value of the eight healthy quadrants for min RI (left), mean RI (center) and max RI (right), according to number of tumour vessels investigated. With increasing number of tumour vessels investigated, there was a higher max RI and a lower min RI in the tumour. As shown in Table 1, the average min RI from all tumours (based on average 3.3 measurements) was 0.629 0.11 S.D. This was significantly lower, than the average min RI from the eight healthy quadrants (0.659 0.08 S.D.) that based on the average of eight quadrants with 1.5 measurements each (p= 0.0001). But if all the measured min RI of the eight quadrants (on average 12 measurements) were taken into account the min RI was 0.549 0.1 S.D. and significantly lower than in the tumour (pB 0.0001). For max RI exactly the opposite correlations were observed. Mean RI was the only parameter showing independency of the number of investigated vessels. The relation of vessel number to RI was corroborated by the same analysis done in those 51 patients which had only one or two tumour vessels as well as by analyzing the RI (min, max, mean) from the first two vessels of the 114 investigated tumours. As shown in Table 1, the min RI did not differ significantly between tumour and healthy breast tissue when the calculation was based on the average of eight quadrants but was significantly higher if the calculation included all measurements within eight quadrants (pB 0.00001).
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193
191
Fig. 1. Differences between RI from tumour area and mean of the eight healthy quadrants (positive difference above, negative difference below zero line) for the parameters min RI (left), mean RI (middle) and max RI (right column) with differentiation for number of vessel cross sections in the tumour area on the abscissa.
4. Discussion Differences in the number of vessels detected may be influenced by several factors as: the impossibility to determine the exact number of vessels using a 2-dimensional assessment, the duration of the examination, the technology used and the experience of the examinator. Taking into consideration our aim to investigate all detectable tumour blood flow, supported by the considerable duration of each examination, we expected a correlation between the number of cross sections detected and the real number of existing vessels.
Irrespective of menopausal state and of the differentiation benign–malignant tumours an increasing number of tumour vessel cross sections correlated with decreasing min RI (p= 0.004), increasing max RI (p= 0.03) and stable mean RI. Paradoxically we observed in the tumour at the same time the lowest (min) RI and the highest (max) RI compared to the average from the eight healthy quadrants. As an increase in perfusion— represented by an increased number of vessels— should be associated with a decreased flow resistance, a general decrease of the min, max and mean RI was to be expected. Lack of uniformity of the results of these three
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193
192
Table 1 Average values and statistical analysis for min, max and mean RI in tumour, average of eight quadrants and complete number of measurements
Mean number of vessels min RI (n= 114) mean RI (n = 114) max RI (n = 114)
Mean number of vessels min RI (n =51)
Mean number of vessels min RI (n = 114)
Average of eight quadrants
Tumour
All measurements within eight quadrants
1.5
3.3
12
0.65 (9 0.08) p= 0.0001 0.68 (9 0.07) p= 0.13 0.70 (9 0.07) pB0.0001
0.62 (90.11) pB0.0001 0.69 (9 0.09) 0.75 (9 0.1) pB0.0001
Average of eight quadrants
Tumour with one or two vessels
All measurements within eight quadrants
1.5
1.6
12
0.66 (9 0.8) p= 0.67
0.65 (90.11) pB0.00001
Average of eight quadrants
Tumour, first two detected vessels
All measurements within eight quadrants
1.5
2.0
12
0.65 (9 0.01) p= 0.63
0.64 (9 0.01) pB0.00001
resistance indices, however, pointed towards a significant influence of vessel number on min RI and max RI. Therefore, these two indices were not the result of the real flow resistance but of mathematical minimizing and maximizing operations. Final proof for the existence of a minimizing–maximizing effect was gained by comparing the different number of measurements in tumour and healthy breast tissue. The results of this study pointed towards the existence of a purely mathematical minimizing effect, which implicitly influences min RI and max RI. The probability to detect a low min RI is strongly influenced by the number of vessel cross sections. So it is not surprising that most published studies about differentiation between benign and malignant tumours (including gynaecological tumours) have found significantly lower min RI in the on average better perfused malignant tumours (Campbell et al., 1992; Kawai et al., 1992; Kurjak et al., 1990; Sohn et al., 1992). The present study questions the validity of min RI for the registration of true flow resistance and as parameter for discrimination
0.54 (9 0.1) 0.68 ( 90.07) 0.80 ( 90.07)
0.55 (9 0.01)
0.54 ( 9 0.01)
between benign and malignant tumours.
References Campbell, S., Bourne, T.H., Reynolds, K., Hampson, J., Royston, P., Whithehead, M.I., Collins, W.P. Role of colour Doppler in an ultrasound-based screening programme. In: Sharp, F., Mason, W.P., Creasman, W., editors. Ovarian Cancer 2: Biology, Diagnosis and Management. London: Chapman and Hall, 1992:237– 247. Cosgrove DO, Kedar RP, Bamber JC, Al-Murrani B, Davey JBN, Fischer C, McKinna JA, Svensson WE, Tohno E, Vagios E, Alsanjari NA. Breast diseases: colour Doppler US in differential diagnosis. Radiology 1993;189:99 –104. Kawai M, Kano T, Kikkawa F, Maeda O, Oguchi H, Tomoda Y. Transvaginal Doppler ultrasound with colour flow imaging in the diagnosis of ovarian cancer. Obstet Gynecol 1992;79:163 – 7. Kurjak A, Jurkovic D, Alfirevic Z, Zalud I. Transvaginal colour Doppler imaging. J Clin Ultrasound 1990;18:227– 31. Madjar H, Pro¨mpeler H, Sauerbrei W, Wolfahrt R, Pfleiderer A. Color Doppler flow criteria of breast lesions. Ultrasound Med Biol 1994;20:849 – 58. McNicholas MM, Mercer PM, Miller JC, McDermott EW, O’Higgins NJ, MacEarlean DP. Colour Doppler sonography in the evaluation of palpable breast masses. Am J
C. Villena-Heinsen et al. / European Journal of Ultrasound 7 (1998) 189–193 Roentgenol 1993;161:765–71. Minasian H, Bamber JC. A preliminary assessment of an ultrasonic doppler method for the study of blood flow in human breast cancer. Ultrasound Med Biol 1982;8:357 – 64.
.
193
Sohn Ch, Grischke EM, Wallwiener D, Kaufmann M, Fournier D, von Bastert G. Die sonographische Durchblutungsdiagnostik gut- und bo¨sartiger Brusttumoren. Geburtsh u Frauenheilk 1992;52:397 – 403.