Marlies Fleck

Electrical impedance scanning for classifying suspicious breast lesions: first results

Abstract. It has long been established that cancer cells exhibit altered local dielectric properties compared with normal cells. Consequently, different electrical conductivity and capacitance are measurable in malignant vs normal tissues. In this study we evaluated the reliability of electrical impedance scanning (EIS), a new technology, for the classification of suspicious lesions: differentiating benign from malignant, and as a primary means of detection of breast cancer. Fifty-two women with 58 sonographically and/or mammographically suspicious findings were examined using electrical impedance scanning. Two different examination modes of TransScan TS2000 (Siemens, Erlangen, Germany), the standard-resolution mode for a routine overview examination, and the targeted high-resolution mode for a local examination of the suspicious lesion were used. All patients were additionally imaged by MR mammography (MRM) and underwent core-biopsy and/or surgical treatment after the EIS examination. With respect to the histopathological findings (29 malignant and 29 benign lesions) 27 of 29 (93.1 %) malignant lesions were correctly identified using the high-resolution mode of EIS, whereas 19 of 29 (65.5 %) benign lesions were correctly identified as benign (10 of 29 benign lesions showed as false-positive findings). Negative and positive predictive values of 90.5 and 73.0 % were observed, respectively. Using the standard-resolution mode 22 of 29 malignancies were correctly detected (sensitivity 75.9 %), whereas 22 of 29 were correctly identified as benign (specificity 72.4 %). Electrical impedance scanning appears to be a promising new technology providing a relatively high sensitivity for the verification of suspicious mammographic and/or sonographic lesions especially using the high-resolution mode for local examinations. Artifacts, such as signals from superficial skin lesions, poor contact, and air bubbles, are currently a limitation.

Tumour detection rate of a new commercially available computer-aided detection system

The aim of this study was to determine the tumour detection rate and false positive rate of a new mammographic computer-aided detection system (CAD) in order to assess its clinical usefulness. The craniocaudal and oblique images of 150 suspicious mammograms from 150 patients that were histologically proven to be malignant were analysed using the Second Look CAD (CADx Medical Systems, Quebec, Canada). Cases were selected randomly using the clinics internal tumour case sampler. Correct marking of the malignant lesion in at least one view was scored as a true positive. Marks not at the location of the malignant lesion were scored as false positives. In addition, mammograms with histologically proven benign masses (n=50) and microcalcifications (n=50), as well as 100 non-suspicious mammograms, were scanned in order to determine the value of false-positive marks per image. The 150 mammograms included 94 lesions that were suspicious due to masses, 26 due to microcalcifications and 30 showed both signs of malignancy. The overall sensitivity was 90.0% (135 of 150). Sensitivity on subsets of the data was 88.7% (110 of 124) for suspicious masses (MA) and 98.2% (55 of 56) for microcalcifications. Eight of 14 false-negative cases were large lesions. The overall false-positive rate was observed as 0.28 and 0.97 marks per image of microcalcifications and masses, respectively. The lowest false-positive rates for microcalcifications and MA were observed in the cancer subgroup, whereas the highest false-positive rates were scored in the benign but mammographically suspicious subgroups, respectively. The new CAD system shows a high tumour detection rate, with approximately 1.3 false positive marks per image. These results suggest that this system might be clinically useful as a second reader of mammograms. The system performance was particularly useful for detecting microcalcifications.

Saline-enhanced Radiofrequency Ablation of Breast Tissue: An In Vitro Feasibility Study

RATIONALE AND OBJECTIVES The feasibility of radiofrequency (RF) ablation for the treatment of breast tumors was investigated in vitro. The best parameters for ablation of breast tissue were chosen. METHODS Saline-enhanced RF ablation was performed in human breast tissue specimens and cow udder tissue. Temperature profiles were measured depending on RF power (20, 28, 36 W) and NaCl infusion rate (15, 30, 60 mL/h) using eight thermocouples. Lesion development was monitored by ultrasound. Thermolysis efficiency was measured by tissue weight determinations before and after ablation. RESULTS After RF ablation of tissue samples, 73.6% turned into a fat/saline emulsion. Ultrasound monitoring showed a cone-shaped hyperechoic area during the first 2 minutes of RF ablation, followed by an irregular expansion of the area. Time-dependent spatial temperature curves were more homogeneous at low infusion rates (15 mL/h). Peak temperatures up to 160 degrees C were measured. CONCLUSIONS Controlled RF ablation of breast tissue is feasible. The irregular expansion of RF lesions in fatty breast tissue is due to liquefied fat. Low saline interstitial infusion rates result in better control of lesioning.

Additional value of electrical impedance scanning: experience of 240 histologically-proven breast lesions

The aim of this study was to quantify the clinical value of using electrical impedance scanning (EIS) as an adjunct to other diagnostic techniques in order to identify cancerous tissue based upon its inherent altered local dielectric properties. 210 consecutive women with 240 sonographically and/or mammographically suspicious findings were examined using EIS. All lesions were histologically-proven. 86/103 malignant and 91/137 benign lesions were correctly identified using EIS (87.8% sensitivity, 66.4% specificity). NPV and PPV of 84.3% and 65.2% were observed, respectively. Excluding cases as defined by a priori criteria, i.e. lesions located deeper than 35 mm, lesions larger than 35 mm, and retroareolar lesions, a sensitivity of 85.5% was observed, and for invasive cancers, 91.7%. The detection rate for ductal carcinoma in situ (DCIS) was poor (57.1%, n=14). By adding EIS to mammography and ultrasound, the sensitivity rose from 86.4 to 95.1%, whereas the accuracy decreased from 82.3 to 75.7%. EIS appears to be of interest as an adjunct to breast diagnostic techniques, performing with a reasonable sensitivity. Further investigations on histomorphological characteristics and the reasons for false-negative findings are essential to gain further knowledge about the bioelectricity of breast lesions, and prove the value of this new technology.

Percutaneous Radiofrequency (rf) Thermal Ablation of Rabbit Tumors Embedded in Fat: A Model for Rf Ablation of Breast Tumors

Boehm T, Malich A, Reichenbach JR, et al. Percutaneous radiofrequency (RF) thermal ablation of rabbit tumors embedded in fat: A model for RF ablation of breast tumors. Invest Radiol 2001;36:480–486. rationale and objectives. To develop an experimental tumor model for RF ablation of breast tumors surrounded by fat and to investigate the minimally invasive treatment of such tumors by saline-enhanced RF ablation monitored by ultrasound (US). methods.Twenty-eight VX2 tumors were implanted into the retroperitoneum of 14 rabbits and monitored by B-mode US at regular intervals of 2 to 3 days. Saline-enhanced RF ablation (25-mm tip length) was performed 16 days after tumor implantation (10-minute treatment time, 28 W, 15 mL/h infusion of 0.9% NaCl, which was increased to 30 mL/h in cases of an impedance increase). Thermal lesion growth was monitored by B-mode US. Treatment was considered complete if no relapse was detectable histopathologically after a follow-up period of up to 3 weeks. results.All tumor implantations were successful, reaching sizes from 5 to 38 mm 16 days after implantation. Tumors >20 mm showed central necrosis on US. Smaller tumors without signs of necrosis required greater needle perfusion to maintain constant needle-to-tissue impedance. Local relapses occurred in 14 of 27 tumors (51.8%), all with tumors >20 mm. In 12 cases, they were already detected sonographically. In 2 cases, “islands” of vital tumor were detected only during histopathological assessment. conclusions.VX2 tumors are implantable into hypovascular adipose tissue with a high success rate and may be used as a model for RF ablation of breast tumors. B-mode US is not suitable for guiding RF ablation of tumors embedded in fat. The method appears to be more successful with smaller tumors.

Electrical impedance scanning as a new imaging modality in breast cancer detection—a short review of clinical value on breast application, limitations and perspectives

Objective. Cancer cells exhibit altered local dielectric properties compared to normal cells, measurable as different electrical conductance and capacitance using electrical impedance scanning (EIS). Therefore, active biocompatible current is applied to the patient for calculation of both parameters taking into account frequency, voltage and current flow. Subjects and methods. 240 women with 280 sonographically and/or mammographically suspicious findings were examined using EIS. All lesions were histologically proven. A lesion was scored as positive, when a focal increased conductance and/or capacitance was measurable using EIS. The lesion was visible as a bright area in a 256 grey-scale computer output. Due to system limitations patients having a pacemaker or pregnant had to be excluded from the study. Results. 91/113 malignant and 108/167 benign lesions were correctly identified using EIS (80.5% sensitivity, 64.7% specificity). NPV and PPV of 83.1% and 60.7% were observed, respectively. Accuracy was 0.73. A wide range of factors can induce false positive results, although by an experienced observer a number of these findings can be detected such as scars, skin alterations, contact artefacts, air bubbles and naevi, hairs and interfering bone. Based upon visibility on ultrasound (194 lesions visible, 86 not visible) significant differences in the detection rate occurred. Histology-dependent detectability rate varied significantly with lowest rate in CIS-cases (50%). Specificity values varied histology-depending, too; probably depending on the rate of proliferation between 75% (inflammatory lesions) and papillomata (50%). Best detectability was observed in malignant lesions with a size between 20 and 30 mm. Further possible applications will be discussed regarding the currently available literature (lymph nodes, salivary glands, mathematical and animal based models). Conclusion. EIS appears to be a promising new additional technology providing a rather high sensitivity for the verification of suspicious breast lesions. Further investigations on histomorphological characteristics of false negative as well as false positive lesions are essential to gain further knowledge about the bioelectricity of breast lesions. Currently high false positive rate and observer-dependence limit clinical usage. r 2002 Elsevier Science B.V. All rights reserved.

Differentiation of breast masses using 3-D sonographic and echo-enhancer-based evaluation of the vascular pattern: initial experiences

To evaluate the potential of combined 3-D B-mode and color Doppler (CD) data sets in the differentiation of breast masses, in 50 patients with histologically proven solid breast lesions, 3-D datasets were acquired. A 3-D display was created and volume calculation of tumors, their periphery and vasculature was performed. Time-intensity curves of enhancement after administration of a contrast agent were analyzed. Volumetry of tumor vasculature yielded no significant differences between malignant and benign tumors regarding vascularization of the center (2.60 vs. 2.88%) and periphery (6.66 vs. 3.78%). Only the mean values for the rise time in the center of the tumor, fibroadenoma (FA): 5.7 s and ductal invasive carcinoma (DIC): 15.8s; p = 0.05, and the time to peak in the periphery, FA: 21.0 s and DIC: 31.6 s; p = 0.03, differed significantly. The 3-D ultrasound (US) technique was of no additional value in differentiating breast masses. The calculation of time-intensity curves after administration of a contrast agent may be helpful in differentiating FA and DIC.

Vacuum-assisted Resection of Malignant Tumors with and without Subsequent Radiofrequency Ablation: Feasibility of Complete Tumor Treatment Tested in an Animal Model

PURPOSE To evaluate the feasibility of vacuum-assisted tumor excision with and without RF ablation for the minimally invasive treatment of small tumors. MATERIALS AND METHODS Twenty VX2 tumors were implanted bilaterally into the spine muscle of 10 rabbits. Tumor excision was performed after tumor sizes reached 10 mm (12-27 d incubation) with use of a vacuum-assisted biopsy device. Three or four directed vacuum-assisted biopsies were performed in angle steps of 30 degrees. In 10 tumors, ultrasound (US)-guided radiofrequency (RF) ablation (8 min, 60 W) was subsequently performed with use of a cooled-tip electrode system. Follow-up US was performed at 3-4-day intervals for as long as 3 weeks after excision/RF ablation. Autopsy and histopathologic analysis were performed. RESULTS The duration of vacuum excision ranged from 12 to 45 minutes (25 min +/- 7). Histologically tumor-free margins in the outer round of the core biopsy specimens were found in only four of 20 cases (20%). Maximum lesion sizes during RF ablation ranged from 18 to 25 mm (20 mm +/- 2.6). Histologic examination of the excision specimens documented tumor-free margins in only three tumors (30%) among the excision-only group and only one (10%) among the combined excision/ablation group. Local recurrences occurred in eight of 10 cases (80%) after vacuum excision alone, whereas recurrence after combined excision and RF ablation occurred only in two of 10 cases (20%; P <.05). CONCLUSIONS Local tumor resection with use of vacuum-assisted biopsy is feasible and promising as a minimally invasive therapy for the treatment of small focal breast neoplasms. Combined excision and RF ablation techniques may reduce the rate of local recurrence considerably.

Contrast-enhanced near-infrared laser mammography with a prototype breast scanner: feasibility study with tissue phantoms and preliminary results of imaging experimental tumors.

Boehm T, Hochmuth A, Malich A, et al. Contrast-enhanced near-infrared laser mammography with a prototype breast scanner: Feasibility study with tissue phantoms and preliminary results of imaging experimental tumors. Invest Radiol 2001;36:573–581. rationale and objectives. Near-infrared (NIR) optical mammography without contrast has a low specificity. The application of optical contrast medium may improve the performance. The concentration-dependent detectability of a new NIR contrast medium was determined with a prototype optical breast scanner. In vivo imaging of experimental tumors was performed. methods.The NIR contrast agent NIR96010 is a newly synthesized, hydrophilic contrast agent for NIR mammography. A concentration-dependent contrast resolution was determined for tissue phantoms consisting of whole milk powder and gelatin. A central part of the phantoms measuring 2 × 2 cm2 without contrast was replaced with phantom material containing 1 &mgr;mol/L to 25 nmol/L NIR96010. The composite phantoms were measured with a prototype NIR breast scanner with lasers of &lgr;1 = 785 nm and &lgr;2 = 850 nm wavelength. Intensity profiles and standard deviations of the transmission signal in areas with and without contrast were determined by linear fit procedures. Signal-to-noise ratios and spatial resolution as a function of contrast concentration were determined. Near-infrared imaging of five tumor-bearing SCID mice (MX1 breast adenocarcinoma, tumor diameter 5–10 mm) was performed before and after intravenous application of 2 &mgr;mol/kg NIR96010. results.Spectrometry showed an absorption maximum of the contrast agent at 755 nm. No spectral shifts occurred in protein-containing solution. Signal-to-noise ratio in the transmission intensity profiles ranged from 1.1 at 25 nmol/L contrast to 28 at 1 &mgr;mol/L. At concentrations <40 nmol/L, no differentiation from the background was possible. The transitional area between the contrast-free edge of the phantom and the central contrast-containing part appeared in the profiles as a steep increase with a width of 4.2 ± 1.8 mm. The experimental tumors were detectable in nonenhanced images as well as contrast-enhanced images, with better delineation after contrast administration. In postcontrast absorption profiles, a 44.1% ± 11.3% greater absorption increase was seen in tumor tissue compared with normal tissue. conclusions.The laser wavelength &lgr;1 of the prototype laser mammography device was not situated at maximum absorption of the contrast agent NIR96010 but on the descending shoulder of the absorption spectrum. This implies a 20% signal loss for contrast detection. Despite the nonideal measurement conditions, concentrations as low as 40 nmol/L were detectable in vitro. In vivo, all tumors were detectable in color-coded nonenhanced scans as well as in contrast-enhanced scans, with better delineation after contrast administration.

Diagnostic evaluation of sonographically visualized breast lesions by using a new clinical amplitude/velocity reference imaging technique (CARI sonography).

RATIONALE AND OBJECTIVES The goal of this study was to evaluate and differentiate breast lesions in patients by sonographic measurements performed using CARI sonography. METHODS Thirty-one patients with 33 histologically proven breast lesions were examined by mammography, conventional ultrasound sonography, and CARI sonography. Investigation with mammography-like positioning was performed in case of CARI sonography. The ratios of the lesion diameters were calculated in a craniocaudal and a mediolateral plane. The results were compared with the results obtained with conventional modalities. RESULTS Breast lesions were detected with the best sensitivity (100%) and a high specificity (86%) using B-mode ultrasound sonography. Mammography resulted in a sensitivity of 92% and a specificity of 91%, whereas the CARI sonography yielded 100% sensitivity and 67% specificity. CONCLUSIONS The differentiation of lesions by measurements performed with CARI sonography resulted in a high sensitivity. The specificity, however, was inferior compared with the other imaging modalities. This may limit the routine application of the technique for clinical diagnoses of breast lesions. However, due to the small number of patients investigated in this pilot study, the full potential should be evaluated in a larger collective of patients.