Search

Objectives Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose. Methods We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device. Results and conclusion Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study. Key Points • Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.

Non-mass enhancement (NME) in breast MRI is the most common feature of ductal carcinoma in situ (DCIS). We sought to evaluate the interobserver variability and positive predictive value (PPV) for malignancy of NME descriptors using the fifth edition BI-RADS lexicon focusing on the newly introduced “clustered ring enhancement” pattern. Breast MRIs of 129 patients who had undergone MRI-guided vacuum-assisted biopsy (VAB) in our institution were reviewed. Studies assessed as NME were classified according to the fifth edition BI-RADS lexicon by two breast radiologists. Consensus was reached by involving a third radiologist. Interobserver variability and PPV for malignancy were assessed. Seventy-two of 129 studies were assessed as NME. The disagreement rate in the first assessment step (mass vs. NME) was low at 9.3% (ĸ = 0.81, 95% confidence interval [CI] 0.71–0.91). The disagreement rate for distribution patterns was 23.6% (ĸ = 0.67, 95% CI 0.54–0.80) and 22.2% (ĸ = 0.69, 95% CI 0.56–0.81) for internal enhancement patterns. Clustered ring enhancement (PPV 53.85, p = 0.038) and segmental distribution (PPV 62.5%, p = 0.028) had the highest malignancy rates among internal enhancement and distribution patterns with a significant result; the combination of clustered ring enhancement and segmental distribution raised the malignancy rate by approximately 4% (PPV 66.67%, p = 0.049). There was a high agreement rate among readers when differentiating NME from mass lesions. The agreement rate was lower when assessing the distribution and internal enhancement pattern descriptors, but still substantial. The descriptors clustered ring enhancement and segmental distribution were significant predictors of malignancy. • Non-mass enhancement is a common morphological feature of non-invasive breast cancer (DCIS) in MRI. Differentiation between potentially malignant and benign changes may be very challenging. • Since clustered ring enhancement and segmental distribution are both significant predictors of malignancy, the awareness of this important finding, combined with high-quality image interpretation skills, may improve the tumor detection rate. • The combination of clustered ring enhancement and segmental distribution increases the positive predictive value for malignancy, which may be relevant for clinical practice.

The superparamagnetic iron oxide tracer Sienna+® was introduced as an alternative to the radioisotope 99Tc Nanocoll to preoperatively mark sentinel lymph nodes in breast cancer. As previously reported, this tracer causes susceptibility artifacts on magnetic resonance imaging (MRI), potentially hampering the diagnostic performance of follow-up breast MRI. This short report illustrates the temporal development of these artifacts in a patient who was followed up at 6, 12, and 18 months after administration of Sienna+® with MRI systems of different magnetic field strengths (1.5 T and 3.0 T) and using an MRI protocol with sequences optimized for artifact reduction. Although the artifacts were severe and predominant at the higher magnetic strength in the early postoperative period, they diminished over time and the image quality could be further improved by adapting the sequences. These findings indicate the possible use of MRI even after administration of a superparamagnetic tracer for post-treatment monitoring in breast cancer. Keywords: Breast neoplasms, Sentinel lymph node, Artifacts, Magnetic fields, Tc 99m nanocolloid, Superparamagnetic nanoparticles

Background The crucial point in making treatment decisions for breast cancer patients is the assessment of tumour aggressiveness. The established prognostic markers may be insufficient to stratify cancer patients into treatment relevant risk groups. Emerging evidence indicates that mechanical properties of cancer cells and their microenvironment that occur on a nanometre scale play a critical role in cancer invasion and metastases. Therefore, detecting these nanomechanical changes could serve as biomarker of cancer aggressiveness. Trial design We conduct a prospective, blinded study in a routine clinical setting. Using minimal invasive breast biopsies we measure the nanomechanical (stiffness) properties of human breast tissue with our atomic force microscope (AFM) based method known as ARTIDIS (Automated and Reliable Tissue Diagnostics). These properties can only be measured using fresh (non-fixed) tissue under physiological conditions (Custodiol transplant buffer). This novel method is based on the use of a micro-fabricated 20nm-sharp tip that indents several thousand individual locations across tissue specimens within 60-180 minutes. Each indentation effectively measures the stiffness of local structures (e.g. cancer cells, extracellular matrix) located under the tip. Thus we obtain a quantitative, biopsy-wide, nanomechanical profile. Post-AFM the same biopsy is used for routine histopathological diagnosis, the current diagnostic gold standard to which the nanomechanical profile is then correlated. Eligibility criteria All women undergoing a minimal invasive breast biopsy (core needle or vacuum assisted biopsy) at the breast centre of the University of Basel. Exclusion criteria: age younger than 18years, necrotic/disintegrated biopsy, and technical limitations Specific aims Our primary endpoint is to differentiate benign from cancerous breast lesions based on their nanomechanical properties. Our secondary endpoint is to subclassify biopsies with cancerous lesions into the current four main breast cancer subgroups (Luminal A, Luminal B, HER2+ and basal-like). Statistical analysis The full dataset will include all patients with valid AFM measurements. Primary analysis: the proportion of true positive results divided by the total number of patients with malignant tumour (sensitivity) will be estimated and presented together with its 95% confidence interval. The histological diagnosis of the same biopsy as analysed by AFM will serve as gold standard. Present accrual and target accrual Present accrual as of June 12, 2017: 200 breast tissue biopsies. Target accrual is 508 biopsies. This will allow for a power of 0.8 and a sensitivity of 90%. Contact information: Rosemarie.Burian@usb.ch Citation Format: Burian R, Appenzeller T, Oertle P, Raez C, Lim R, Forte S, Dellas S, Münst S, Obermann E, Plodinec M. Atomic force microscopy (AFM) - a novel nanotool for cancer diagnostics: A prospective, blinded study of nanomechanical profiling of human breast tissue as a potential biomarker for stratifying low- and high-risk breast cancer subtypes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-05.

Rationale The gold standard for detection of axillary sentinel lymph nodes uses injection of a radioisotope (99Tc Nanocoll). As an alternative to this method, a magnetometer detecting the superparamagnetic tracer Sienna+® can be applied for detection of sentinel lymph nodes. The goal of this study was to determine whether interpretation of breast MRI is impaired by Sienna+® tracer residues in the operated breast and axillary lymph nodes after a sentinel procedure using this tracer. Patients and methods 34 patients who received the Sienna+® tracer for marking the sentinel node were invited to undergo a follow-up breast MRI. Native MR images were obtained from breast and axilla. The breast MRIs were evaluated by two independent breast radiologists for Sienna+® tracer related artefacts and for the degree of impairment of the MR imaging. Results 24 of the 34 invited patients took part in this study. The mean time since injection of Sienna+® was 42 months (40.6–45.4 months). Two patients had bilateral surgery with injections in both breasts, leading to a total of 26 separate cases. One case had to be excluded due to breathing artefacts. In 10 cases (40%), impaired imaging was found. In three cases (12%), the MRI scan reading was impossible due to Sienna+® tracer residues, the other 12 cases (48%) showed no restriction. In the subgroup of patients treated with breast conserving surgery, tracer residue artefacts were found in 13 of 17 patients (76.5%). Conclusion To our knowledge, in this study for the first time MR feasibility after Sienna injection was investigated. Sienna+® impaired breast MRI after a mean follow-up time of 42 months in half of the cases. Further research is needed to investigate time and field-strength dependency of tracer detectability as well as the diagnostic impact of these artifacts on contrast-enhanced imaging in a clinical setting.

To investigate changes in breast density (BD) during the menstrual cycle in young women in comparison to inter-breast and -segment changes as well as reproducibility of a novel Speed-of-Sound (SoS) Ultrasound (US) method. SoS-US uses a conventional US system with a reflector and a software add-on to quantify SoS in the retro-mammillary, inner and outer segments of both breasts. Twenty healthy women (18–40 years) with regular menstrual cycles were scanned twice with two weeks in-between. Three of these were additionally measured twice per week for 25 days. Average SoS (m/s) and ΔSoS (segment-variation SoS; m/s) were measured. Variations between follicular and luteal phases and changes over the four-week period were assessed. Inter-examiner and inter-reader agreements were also evaluated. Variances between cycle phases, examiners and readers were compared. No significant SoS difference was observed between follicular and luteal phases for the twenty women (P = .126), and between all different days for the three more frequently measured women (P = .892). Inter-reader (ICC = 0.999) and inter-examiner (ICC = 0.990) agreements were high. The SoS variance due to menstrual variations was not significantly larger than the inter-examiner uncertainty (P = .461). Inter-reader variations were significantly smaller than menstrual and examiner variations (P < .001). SoS-US showed high inter-examiner and inter-reader reproducibility. The alterations during the menstrual cycles were not significantly larger than the confidence interval of measurements., Medicine, 98 (25)

Purpose: The question of overtreatment of ductal carcinoma in situ (DCIS) was raised because a significant proportion of especially low-grade DCIS lesions never progress to invasive cancer. The rationale for the present study was to analyze the value of stereotactic vacuum-assisted biopsy (VAB) for complete removal of DCIS, focusing on the relationship between the absence of residual microcalcifications after stereotactic VAB and the histopathological diagnosis of the definitive surgical specimen. Patients and Methods: Data of 58 consecutive patients diagnosed with DCIS by stereotactic VAB in a single breast center between 2012 and 2017 were analyzed. Patient records from the hospital information system were retrieved, and mammogram reports and images as well as histopathology reports were evaluated. The extent of microcalcifications before and after biopsy as well as the occurrence of DCIS in biopsy and definitive surgical specimens were analyzed and correlated. Results: There was no correlation between the absence of residual microcalcifications in the post-biopsy mammogram and the absence of residual DCIS in the final surgical specimen (p = 0.085). Upstaging to invasive cancer was recorded in 4 cases (13%) but occurred only in the group that had high-grade DCIS on biopsy. Low-grade DCIS was never upgraded to high-grade DCIS in the definitive specimen. Conclusions: The radiological absence of microcalcifications after stereotactic biopsy does not rule out residual DCIS in the final surgical specimen. Since upstaging to invasive cancer is seen in a substantial proportion of high-grade DCIS, the surgical excision of high-grade DCIS should remain the treatment of choice.

Clinical treatment of breast cancer is successful. What remains a challenge for individualized therapy is the prediction of which cancer responds to which treatment. Emerging evidence indicates that mechanical alterations on a (sub-) cellular level are markers of cancer aggressiveness. Detecting these could serve as biomarker and help optimize cancer diagnosis, therapy choice, and patient follow-up. We developed a diagnostic platform called ARTIDIS (Automated and Reliable Tissue Diagnostics) based on atomic force microscopy (AFM)-type nanomechanical testing. ARTIDIS uses a 20-nanometer-sharp tip measuring 10'000 miniscule indentation across the biopsy's surface and quantifies stiffness on a molecular level. The relative size and distribution of stiffness values is integrated into a data analytics tool that systematically analyses tissue biomechanics in correlation to clinical parameters, histological prognostic markers, and treatment yielding prognostic and predictive value. To demonstrate ARTIDIS' clinical utility for diagnosis and development of prognostic and predictive biomarkers we conducted a prospective blinded clinical study on 545 patients. All patients undergoing a core needle or vacuum biopsy of the breast qualified. Within the routine clinical workflow, ARTIDIS analyzed fresh biopsies in a physiological solution preserving the biopsy's viability for histological and genetic analysis. Per patient, one representative biopsy was measured, marked and reunited with the patient's other biopsies for standard histological procedure. In total, 583 biopsies from N=545 patients were analyzed: 62.1% were B1-B4 (normal, benign, of uncertain malignant potential, or suspicious); a third (36.9%) malignant (B5a-B5d), and six specimens (1%) not assignable. Half of all B5b lesions were Luminal B, followed by Luminal A, Luminal B-like, HER2-positive or triple negative. The analysis of the primary endpoint (N=520 patients qualified, N=3 were excluded due to missing information) demonstrated ARTIDIS' ability to detect cancer in all samples including lesions with We could separate more aggressive cases within the Luminal B subtype (CI 95%; sensitivity 83%, specificity 82%, AUC = 0.86). Secondary analysis also indicated a similarity between the majority of B3 (uncertain) and B2 (benign) lesions and distinct differences from all B5a and B5b, which could help reduce overtreatment of B3 lesions. This large prospective single center study demonstrated ARTIDIS' ability to differentiate benign from malignant lesions and to further subclassify specific breast cancer subtypes. In addition, Luminal B cancers exhibited nanomechanical profiles associated with better or worse prognosis and treatment outcome. The final analysis results provide cutoffs that will be assessed in the upcoming large multicenter prospective trial. Finally, this study helped to determine clinical utility of nanomechanical characterization of breast and other solid cancers for prediction and treatment optimization. Citation Format: Rosemarie Burian, Ahmed Jizawi, Flora Scott, Sabine Schädelin, Christian Raez, Simone Muenst-Soysal, Tatjana Vlaijnic, Ellen Obermann, Sophie Dellas, Serafino Forte, Zlatko Marušić, Tobias Appenzeller, Philipp Oertle, Nam Seung-Zln, Gregory Zaugg, Milan Liepelt, Gabriel Zihlman, Roderick Lim, Marko Loparic, Marija Plodinec. First clinical validation of the physical biomarker based on the nanomechanical tissue profiling for rapid breast cancer diagnosis, prognosis and predication of treatment outcome [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-273.

Purpose In addition to absorption imaging, grating interferometry-based mammography (GIM) is capable of detecting differential-phase and scattering signals. In particular, the scattering signal can enable a quantifiable characterization of breast lesions. The purpose of this study was to determine if suspicious microcalcifications associated with benign or malignant lesions can be discriminated based on their absorption and scattering properties. Materials and Methods In this prospective, ethically approved study, 62 patients (mean age 60 y, range 39–89) with suspicious microcalcifications, who underwent stereotactic biopsies, were included. Biopsies were measured with an experimental GIM device and the ratios of the scattering and absorption signal (R-value) for microcalcifications were calculated. The mean R-values for benign and malignant lesions associated with microcalcifications were compared with the final histopathological diagnosis using a t-test. Results Twenty of the 62 participants had microcalcifications associated with malignancy. Comparing the two largest histopathological sub-groups of fibrosis (n = 23) vs. ductal carcinoma in situ (n = 15) resulted in an average R-value of 4.08 for benign and 2.80 for malignant lesions; p = 0.07. All microcalcifications associated with malignancy had an R-value below 4.71. Excluding microcalcifications with an R-value above this threshold would result in an 11 % reduction of false positives. Conclusion The novel GIM modality has the potential to non-invasively characterize microcalcifications and might aid in the discrimination of benign from malignant lesions in fresh biopsy samples.

Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose.We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device.Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study.• Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.

Grating interferometry mammography (GIM) is an experimental breast imaging method at the edge of being clinically implemented. Besides attenuation, GIM can measure the refraction and scattering of x-rays resulting in differential phase contrast (DPC) and dark-field (DF) images. In this exploratory study, we assessed the feasibility of using microbubbles as a contrast agent in GIM. Two millilitres of microbubbles and iodine were respectively injected into ex vivo breast phantoms, consisting of fresh chicken breasts. Native and postcontrast images were acquired with a clinically compatible GIM setup, operated at 38 kVp, 14-s acquisition time, and with a dose of 1.3 mGy. The visibility of the contrast agents was analysed in a side-by-side comparison by three radiologists. The contrast-to-noise-ratio (CNR) was calculated for each contrast agent. We found that both contrast agents were judged to be visible by the readers. The mean CNR was 3.1 ± 1.9 for microbubbles in DF and 24.2 ± 6.5 for iodine in attenuation. In conclusion, this is a first proof-of-mechanism study that microbubbles could be used as a contrast agent in clinically compatible GIM, due to their scattering properties, which implies the potential use of a contrast agent with a high safety profile in x-ray-based breast imaging. ISSN:2509-9280

BackgroundMultimodal ultrasound tomography (MUT) is a promising new three-dimensional imaging technology for breast cancer detection without ionizing radiation or need for tissue compression. It of...

To assess feasibility and diagnostic accuracy of a novel hand-held ultrasound (US) method for breast density assessment that measures the speed of sound (SoS), in comparison to the ACR mammographic (MG) categories. ACR-MG density (a=fatty to d=extremely dense) and SoS-US were assessed in the retromamillary, inner and outer segments of 106 women by two radiographers. A conventional US system was used for SoS-US. A reflector served as timing reference for US signals transmitted through the breasts. Four blinded readers assessed average SoS (m/s), ΔSoS (segment-variation SoS; m/s) and the ACR-MG density. The highest SoS and ΔSoS values of the three segments were used for MG-ACR whole breast comparison. SoS-US breasts were examined in

Mechanical properties and physical interactions of cells and their microenvironment that occur at nanometre scale play a critical role in cancer progression and metastatic dissemination (https://physics.cancer.gov). Nanomechanical profiling of breast tissue enables fast and precise cancer diagnosis. Detecting extreme viscoelastic (soft) cancer cells in biopsies provides a direct biomarker of cancer aggressiveness (Plodinec et. al., 2012). In an ongoing single centre clinical trial conducted in a routine clinical setting we distinguish benign from cancerous breast lesions within 2.5 hours using an atomic force microscope (AFM)-based method known as ARTIDIS. ARTIDIS employs a micro-fabricated 20nm-sharp tip which indents 10,000 locations/sample to measure the stiffness of cellular and matrix structures. In a comprehensive web-based platform we collect, verify and analyze these 2.54 millions of AFM indentations in relation to over 100 clinical parameters /patient using artificial intelligence. In our interim analysis of core needle and vacuum biopsies (N=254), 34 samples were classified as B1 (normal); 127 as B2 (benign); 12 as B3 (uncertain malignant potential); 0 as B4 (suspicious); 18 as B5a (ductal carcinoma in situ), and 58 as B5b (malignant). The diagnostic AFM ROC curve of B1 and B2 lesions vs. all B5 lesions (CI 95%; 100% sensitivity, 90% specificity, AUC = 0.98) demonstrated ARTIDIS outstanding ability to detect cancer in samples with >80% neoplastic tissue. An analysis including lesions with Citation Format: Rosemarie Burian, Ahmed Jizawi, Gabriel Zihlmann, Tobias Appenzeller, Philipp Oertle, Christian Raez, Roderick Y. Lim, Serafino Forte, Sophie Dellas, Simone Muenst, Tatjana Vlajnic, Ellen Obermann, Maria Ricci, Kevin Grimm, Ferdinand Niedermann, Marko Loparic, Marija Plodinec. A prospective, double-blinded clinical study using atomic force microscopy for fast diagnosis and subtyping of low and high-risk breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3140.

A 52-year-old patient referred to our hospital for a screening mammogram showed a suspicious new architectural distortion. Previously, a fibroadenolipoma within the right breast was diagnosed clinically and radiologically. Further work-up with tomosynthesis, magnetic resonance imaging, and magnetic resonance-guided biopsy showed an invasive ductal carcinoma within the fibroadenolipoma, which are usually benign breast lesions not associated with malignancy. This case report offers a review of the literature and a discussion of signs, which should alert the radiologist.

11618 Background: Assessment of tumor aggressiveness is crucial when making treatment decisions. Established prognostic markers may be insufficient to stratify cancer patients into treatment relevant risk groups. Emerging evidence indicates mechanical properties of cancer cells and their microenvironment play a vital role in cancer invasion and metastases. Detecting and measuring these nanomechanical changes could be a marker of cancer aggressiveness. Methods: We developed an atomic force microscope (AFM) based method: ARTIDIS (Automated and Reliable Tissue Diagnostics) for measuring nanomechanical properties of human tissue biopsies. These were performed on fresh, non-fixed tissue under physiological conditions. This novel method uses a micro-fabricated 20nm tip indenting and measuring stiffness of thousands of locations within 60-180minutes. This quantitative, biopsy-wide, nanomechanical profile strongly correlates to the tissue's biological composition. Post-AFM this biopsy is analyzed by pathology. We sought to differentiate benign from cancerous lesions based on nanomechanical properties; then link the cancerous nanomechanical profiles prospectively to the clinical outcomes. Results: Our results demonstrate the first AFM based nanomechanical profiling to detect aggressive breast cancer subtypes using fresh tissue in a clinical setting. We have shown that nanomechanical profiles of human breast cancer biopsies display stiffness profiles distinct from surrounding normal tissue. Breast cancer subtypes were distinguishable by their nanomechanical properties only. We have discovered specific nanomechanical profiles of tumor subtypes likely to metastasize. When the primary tumor displayed the same soft nanomechanical profile as adjacent tissue, this was associated with positive nodal status. Conclusions: Our results demontrate nanomechanical profiling is a fast and sensitive method to stratify malignant biopsies into relevant subgroups in a clinical setting. Relative stiffness and distribution values provide a nanomechanical profile indicating cancer aggressiveness. This will help optimize specific cancer diagnosis, orientate therapy choice and support patient follow up.

Phase-contrast mammography is a rising technology where, in addition to X-ray absorption, images show phase and dark-field contrast. Although the use of biopsy markers constitutes a fundamental task in breast examinations, there has not been any investigation concerning appropriate clips for this technology. We studied the suitability of three markers (Tumark, Somatex Medical Technologies; Hydromark, Mammotome; and Mammostar, Mammotome) for this modality on a laboratory source setup using a chicken breast phantom. The first two clips appeared to be innocuous, whereas Mammostar showed the potential that the non-metallic portion only could be used as a marker for this technique.

Bladder cancer is the fourth most common malignancy among men in the Western world. Bone metastasis occurs in 27 % of the cases. Usually, the location is the spine. The present report describes the first case of a proven distant bone metastasis to the acromion from a urinary bladder carcinoma in a patient with shoulder pain.