Martin Freesmeyer

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.

Normative Values of Bone Parameters of Children and Adolescents Using Digital Computer-Assisted Radiogrammetry (DXR)

PURPOSE To verify whether estimation of bone mineral density (BMD) using digital X-ray radiogrammetry (DXR) is possible on children and to determine normative values of both such a DXR-BMD estimate and a corresponding metacarpal index (DXR-MCI) on. PATIENTS AND METHODS In retrospect, X-rays were selected of the hands of 200 healthy Caucasian children (120 boys and 80 girls, aged 4-18 yr). The involved children were selected among a larger group of children submitted to the surgical department of our institute for evaluation of a suspected fracture after an occurred trauma. All children with a verified fracture or a chronic bone-related disease, including bone age retardation or acceleration, were excluded from the study. Furthermore, only conventional X-rays with the same film and capture parameters were included. The images were scanned and analyzed using the Pronosco X-posure system V.2 (Sectra Pronosco, Denmark). DXR-BMD, DXR-MCI, and a porosity index (DXR-PI) were automatically calculated using the midshafts of the metacarpals II-IV. Mean values of DXR-BMD and DXR-MCI were calculated separately for girls and boys in 2-yr intervals. RESULTS In the present study the system has been demonstrated to be capable of calculating DXR-BMD from conventional X-rays of the hand from children down to approx 6 yr of age. This ability depended somewhat on the diameter and the length of the involved metacarpals. The success rate was higher for large bones than for small bones. The system succeeded in analyzing the images of 110 boys and 68 girls. Values of DXR-BMD were observed to increase with age from 0.40 g/cm2 to 0.62 g/cm2 in the male group and from 0.39 g/cm2 to 0.54 g/cm2 in the female group. Girls aged 11-12 yr had a higher DXR-BMD than did boys, corresponding to the earlier entry to puberty of girls. Standard deviations (SDs) reached values of up to 0.05 g/cm2. DXR-MCI increased with age from 0.36 to 0.47 for boys and from 0.34 to 0.49 for girls with a maximum SD of 0.06. The correlation between DXR-BMD and age was r=0.83 and r=0.84 for boys and girls, respectively. The corresponding correlations for DXR-MCI was lower, with observed correlations of r=0.63 (boys) and r=0.68 (girls), respectively, with p<0.01 in all cases. The DXR-PI did not reveal a significant correlation to age (r=-0.31 and r=0.04. respectively) and showed SDs marginally higher than the calculated mean values. CONCLUSION The newly available DXR-methodology seems to offer the ability to determine DXR-BMD and DXR-MCI in children starting with a bone age of 6. This possibility may be of special relevance for children suffering from chronic bone diseases that require repeated X-rays of the hand (e.g. to determine bone age). The acquired normative data suggest that the measurements are of clinical value owing to low age-dependent variability (SDs) relative to an observed high increase with age. The clinical value of the porosity index (DXR-PI) remains uncertain and is limited owing to a high inter-individual variability.

Early Dynamic 18F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions

In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) 18F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED 18F-FDG PET/CT efficacy in this setting but applied a larger-than-standard 18F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Methods: Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED 18F-FDG PET for 240 s, starting with 18F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time–activity curves. Results: All 34 lesions were identified by early focal 18F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. Conclusion: This pilot study provided proof of principle that our simplified ED 18F-FDG PET/CT protocol includes endpoints that effectively detect HCC hypervascularization; this finding suggests that the protocol can be used routinely.

Hybrid Integration of Real-time US and Freehand SPECT: Proof of Concept in Patients with Thyroid Diseases

PURPOSE To report an initial experience regarding the feasibility and applicability of quasi-integrated freehand single photon emission computed tomography (SPECT)/ultrasonography (US) fusion imaging in patients with thyroid disease. MATERIALS AND METHODS Local ethics committee approval was obtained, and 34 patients were examined after giving written informed consent. After intravenous application of 75 MBq of technetium 99m pertechnetate, freehand three-dimensional SPECT was performed. Data were reconstructed and transferred to a US system. The combination of two independent positioning systems enabled real-time fusion of metabolic and morphologic information during US examination. Quality of automatic coregistration was evaluated visually, and deviation was determined by measuring the distance between the center of tracer distribution and the center of the US correlate. RESULTS All examinations were technically successful. For 18 of 34 examinations, the automatic coregistration and image fusion exhibited very good agreement, with no deviation. Only minor limitations in fusion offset occurred in 16 patients (mean offset ± standard deviation, 0.67 cm ± 0.3; range, 0.2-1.0 cm). SPECT artifacts occurred even in situations of clear thyroid findings (eg, unifocal autonomy). CONCLUSION The freehand SPECT/US fusion concept proved feasible and applicable; however, technical improvements are necessary.

Real-time ultrasound and freehand-SPECT. Experiences with sentinel lymph node mapping.

UNLABELLED Aim of this work is to report first experiences of the feasibility and applicability of a hybrid freehandSPECT/ultrasound (fh-SPECT/US) imaging concept, with regard to SLN imaging, in patients with breast cancer and malignant melanoma. PATIENTS, METHODS 18 patients with breast cancer or malignant melanoma received standard SLN scintigraphy. Following this, fh-SPECT using declipse®SPECT (SurgicEye, Munich, Germany) was performed, a handheld-gamma camera-based method to visualize activity distribution within a region of interest as a cross-sectional data set. These data were transferred to an ultrasound device and sensor-navigated ultrasound was performed combining fh-SPECT data with ultrasound images, displaying superimposed images. Quality of fh-SPECT and co-registration accuracy was assigned to one of four categories and occurrence of artefacts was assessed. RESULTS In 4/18 examinations, there was a no deviation regarding co-registration of both data sets. For 9/18 patients, there was a deviation of <1 cm (mean 0.7±0.3 cm, range 0.3-1.0 cm). For 3/18 patients, a deviation >1 cm was present (mean 1.7±0.3 cm, range 1.5-2.0 cm). In 2/18 examinations no lymph node was found in the region of highest activity. Fh-SPECT reconstruction artifacts occurred in 6/18 examinations. CONCLUSION The fusion imaging concept combining SLN information with ultrasound images presented here proves to be feasible and technically successful. However, significant technical limitations were shown in fh-SPECT quality and fusion precision. Subject to technical optimisation of SPECT quality and co-registration, a meaningful contribution to the preoperative planning of lymph node therapy is imaginable. Thus, fundamentally a preoperative histological examination by fh-SPECT/US-guided biopsy is possible.

Differential Diagnosis of Thyroid Nodules via Real-Time PET/Ultrasound (US) Fusion in a Case of Co-existing Medullary Thyroid Cancer and Adenoma

A 52-year-old woman presented with apparent carcinoid syndrome. Gallium 68 (Ga)-DOTATOC positron emission tomography (PET)/computed tomography (CT) found a 2.5-cm somatostatin receptor (SR)positive nodule in the left thyroid lobe. Basal serum calcitonin was 5184 ng/L, TSH was 0.63 mU/L, and free T4 was 16.98 pmol/L, so medullary thyroid cancer was suspected. Ultrasonography (Figure 1, A and B), F-fluorodeoxyglucose (FDG) PET/CT, and iodine 124 (I) PET/ CT, performed to allocate thyroid nodules to GaDOTATOC PET findings and exclude metastases, revealed an adjacent nodule 1 cm (Figures 1 and 2), believed to be adenoma. The patient provided informed consent for all procedures. To unambiguously characterize the nodules, we used a magnetic navigation system (VNav; GE Healthcare) to perform live fusion of metabolic/functional images acquired through PET and morphological images obtained with ultrasound (PET/ultrasonography) (1). Live fusion recently was reported to be a problem-solving tool in cases of unclear PET findings (2); although CT shows anatomical landmarks facilitating PET image interpretation, ultrasonography offers superior soft-tissue resolution to that of CT. Moreover, real-time coregistration allows immediate, interactive investigation. PET/CT data are acquired according to standard protocol, then loaded onto an ultrasonography system located in a separate room; images are aligned using anatomical landmarks, and three-dimensional PET/CT views are then automatically reoriented and fused to live ultrasonographic images according to ultrasound probe positioning (3) (Figure 2, A–C, and Movie 1). After thyroidectomy, histology confirmed our hypothesis regarding the lesions. Real-time fusion of PET/ultrasonography images thus differentiated an F-FDG-positive, I-negative, and SR-positive thyroid nodule, which proved to be medullary thyroid cancer, from an adjacent F-FDG-negative, I-positive, and SR-negative nodule, which turned out to be a compensated autonomous adenoma (Figure 2).

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

Purpose of the ReportThe standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. Patients and MethodsTwenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of “hot spots” with/without central photopenia and “cold spots” detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. Results124I-PET detected significantly more “hot spots” with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more “cold spots” than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). Conclusions124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.

Circulating epithelial cells in patients- with thyroid carcinoma. Can they be identified in the blood?

GOAL To investigate whether circulating epithelial cells (CEC) recognized via the epithelial cell adhesion molecule (EpCAM) can be identified in the blood of patients with thyroid carcinoma, given that CEC have already been detected in other types of carcinoma and are considered a potential marker of tumour dissemination. PATIENTS, METHODS Blood samples of patients with active differentiated thyroid carcinoma (DTC) (n = 50) were compared to samples of patients with: a) recent surgical excision of a thyroid carcinoma (postOP-DTC) (n = 16); b) athyreotic, tumour-free status after radioiodine ablation (AT-DTC) (n= 33); and c) benign thyroid diseases (BTD) (n = 51). Samples of volunteers with normal thyroid parameters (NT) (n = 12) were also investigated. Cells from EDTA-blood were subjected to erythrocyte lysis, isolated by centrifugation, and incubated with a fluorescence-labeled antibody against EpCAM. The numbers of vital cells were counted via fluorescence microscopy. RESULTS CEC were identified in all groups, with the postOP-DTC group showing the highest mean CEC numbers of all groups. The DTC group had significantly higher CEC numbers than the NT group, and numerically higher numbers than the other groups, although not reaching statistical significance. Within the DTC group there was a correlation between levels of serum thyroglobulin and numbers of CEC (r = 0.409, p = 0.003). CONCLUSIONS High CEC numbers were not specific to thyroid carcinoma. The methodology used here, based on a single measurement does not allow to identify severe forms of DTC, emphasizing the need of longitudinal measurements throughout therapy. Detection and characterization of tumour thyroid cells in circulation should be based on additional consideration of tissue-specific characteristics.

Interventionelle MR-Mammographie: Manipulatorgestützte Biopsie und interstitielle Lasertherapie von Tumoren der weiblichen Brust

The present study investigated the clinical application of magnetic resonance (MR)-guided breast interventions, such as manipulator-assisted large core breast biopsy (LCBB) inside a 1.5 T whole-body magnet and MR-guided interstitial laser therapy (ILT). Sixteen patients underwent LCBB and 1 additional patient underwent 4 sessions of ILT of a recurrent undifferentiated lymph node metastasis in the axilla using a Nd-YAG laser (1064 nm). Temperature changes of the tumor tissue during ILT were monitored using phase images of a gradient echo sequence (GRE) (TR/TE/FA = 25/12/30). In 5 patients the biopsy findings were histopathologically confirmed after open surgery. In 3 patients, the biopsy missed one tubular and one ductal carcinoma; one invasive carcinoma was underestimated. Eight patients with benign findings are still in the follow-up period. The heating zone during ILT was well delineated on subtracted phase images. No severe adverse events were observed with LCBB or ILT. MR-guided breast biopsies are feasible with the manipulator system inside a whole-body 1.5 Tesla MR scanner. GRE information is suitable for therapy monitoring during ILT within the tumor. Further studies are necessary to evaluate the accuracy of the manipulator system and the efficacy of ILT in the treatment of breast lesions.

Early dynamic 18F-FDG PET/CT to diagnose chronic osteomyelitis following lower extremity fractures. A pilot study.

AIM The study investigates whether early dynamic PET/CT (edPET/CT) using 18F-fluorodeoxyglucose (FDG) discriminates between affected versus non-affected sites in patients with complicated, protracted fracture healing and suspected COM in the lower extremities. PATIENTS, METHODS In nine consecutive patients (1 woman, 8 men; age 54 ± 13 years), before standard late FDG-PET/CT, altogether 10 edFDG-PET/CT examinations were performed in list mode over 5 min starting with radiopharmaceutical injection. Eight consecutive time intervals (frames), four 15-s, then four 60-s, were reconstructed. For every patient, several volumes-of-interest were selected. To measure early FDG influx and accumulation, maximum and mean ed standardized uptake values (respectively, edSUVmax, edSUVmean) were calculated in each volume-of-interest during each frame. Results were compared between affected and non-affected (contralateral) bone. RESULTS Starting in the 31-45s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean than did the healthy contralateral region. In conventional PET/CT, affected bone areas also significantly differed from non-affected contralateral regions. CONCLUSION This pilot study suggests that edFDG-PET may offer a less time consuming add on to standard FDG-PET/CT while being equally accurate. The results should be validated prospectively in larger trials.