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In oncology, the feasibility of Cerenkov luminescence imaging (CLI) has been assessed by imaging superficial lymph nodes in a few patients undergoing diagnostic

Accurate delineation of the boundary between cancerous and healthy tissue during cancer resection surgeries is important to ensure complete removal of cancerous cells while preserving healthy tissue. Labelling cancer cells with radiotracers, and then using a probe during surgery to detect the radiotracer distribution, is a potential solution for accurate tumour localisation and hence better surgical outcomes. This work explores the feasibility of using deep learning to reconstruct a radiotracer distribution from data acquired by an intraoperative probe. The probe’s sensor array outputs (SAOs), obtained by scanning the probe over a region of interest, are supplied to the deep network, which then outputs a reconstructed radiotracer distribution for the region of interest. This initial work demonstrates that the deep network used here, a convolutional encoder decoder (CED), can successfully reconstruct simulated 2D radiotracer distributions from synthesised input data. However, the network was unable to generalise reliably when tested with count levels not present in the training set. Therefore the network must be trained with desired count levels or else should include estimation of epistemic uncertainty to avoid misleading outcomes. We also show that test-time augmentation can improve reconstructed image quality, and hence can also be used to reduce the amount of training data required.

Radioguided surgery (RGS) techniques have been developed to enable more accurate and selective nodal identification and dissection in cancer patients [1]. The most well-established application of RGS is sentinel lymph node biopsy (SLNB), and use of a technetium- 99m (99mTc)-labelled radiotracer in combination with a fluorescent or blue dye is the recommended technique for optimal sentinel lymph node (SLN) detection in those malignancies [2-3]. Minimally-invasive radioguided SLN procedures currently rely on the use of rigid laparoscopic gamma probes (RLGPs), which have limited manoeuvrability and control due to their rigidity and dimensions. To address these limitations, miniaturised ‘drop-in’ gamma probes have been developed by different groups, with each probe having different design and performance features [4]. Our group has developed the SENSEI® drop-in gamma probe in collaboration with Lightpoint Medical Ltd. The probe can be used in both robotic and laparoscopic surgery due to its design. Here we present the design and technical characteristics of the device, the interim clinical trial results in prostate cancer (PCa) and the planned clinical study in rectal cancer (RCa).

Introduction: Cerenkov luminescence imaging (CLI) is a novel imaging technology that might have the ability to assess surgical margins intra-operatively during prostatectomy using Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11). This study evaluates the accuracy of CLI compared to histopathology and as exploratory objective investigates the characteristics of the identified chemiluminescence signal. Materials and Methods: After intravenous injection of a mean 68Ga-PSMA-11 activity of 69MBq intraoperatively, all excised specimens were imaged with CLI. Areas of increased signal were marked for histopathological comparison and scored for likelihood of being a positive surgical margin (PSM) using a 5-point Likert scale. In addition, the chemiluminescence signal was investigated in three radioactive and three non-radioactive specimens using CLI. Results: In 15 patients, the agreement between CLI and histopathology was 60%; this improved to 83% when including close surgical margins (≤1mm). In six hotspots, CLI correctly identified PSMs on histopathology, located at the apex and mid-prostate. In all 15 patients an increased signal at the prostate base was observed, without the presence of the primary tumor in this area in eight patients. This chemiluminescence signal was also observed in non-radioactive prostate specimens, with a half-life of 48±11min. The chemiluminescence hampered the visual interpretation of four PSMs at the base. Conclusion: CLI is able to correctly identify margin status, including close margins, in 83% of the cases. The presence of a diathermy-induced chemiluminescent signal hampered image interpretation, especially at the base of the prostate. In the current form, CLI is most applicable to detect PSMs and close margins in the apex and mid-prostate.

Surgical instrument segmentation and depth estimation are crucial steps to improve autonomy in robotic surgery. Most recent works treat these problems separately, making the deployment challenging. In this paper, we propose a unified framework for depth estimation and surgical tool segmentation in laparoscopic images. The network has an encoder-decoder architecture and comprises two branches for simultaneously performing depth estimation and segmentation. To train the network end to end, we propose a new multi-task loss function that effectively learns to estimate depth in an unsupervised manner, while requiring only semi-ground truth for surgical tool segmentation. We conducted extensive experiments on different datasets to validate these findings. The results showed that the end-to-end network successfully improved the state-of-the-art for both tasks while reducing the complexity during their deployment.

Purpose Currently, approximately 11–38% of prostate cancer (PCa) patients undergoing radical prostatectomy have a positive surgical margin (PSM) on histopathology. Cerenkov luminescence imaging (CLI) using 68Ga-prostate-specific membrane antigen (68Ga-PSMA) is a novel technique for intraoperative margin assessment. The aim of this first-in-man study was to investigate the feasibility of intraoperative 68Ga-PSMA CLI. In this study, feasibility was defined as the ability to distinguish between a positive and negative surgical margin, imaging within 45 min and low radiation exposure to staff. Methods Six patients were included in this ongoing study. Following perioperative i.v. injection of ~ 100 MBq 68Ga-PSMA, the prostate was excised and immediately imaged ex vivo. Different acquisition protocols were tested, and hotspots on CLI images from the intact prostate were marked for comparison with histopathology. Results By using an acquisition protocol with 150 s exposure time, 8 × 8 binning and a 550 nm shortpass filter, PSMs and negative surgical margins (NSMs) were visually correctly identified on CLI in 3 of the 5 patients. Two patients had a hotspot on CLI from cancer Conclusion Overall, the study showed that 68Ga-PSMA CLI is a feasible and low-risk technique for intraoperative margin assessment in PCa. The remaining patients in this ongoing study will be used to assess the diagnostic accuracy of the technique. Trial registration: NL8256 registered at www.trialregister.nl on 04/11/20109.

Purpose In surgical oncology, complete cancer resection and lymph node identification are challenging due to the lack of reliable intraoperative visualization. Recently, endoscopic radio-guided cancer resection has been introduced where a novel tethered laparoscopic gamma detector can be used to determine the location of tracer activity, which can complement preoperative nuclear imaging data and endoscopic imaging. However, these probes do not clearly indicate where on the tissue surface the activity originates, making localization of pathological sites difficult and increasing the mental workload of the surgeons. Therefore, a robust real-time gamma probe tracking system integrated with augmented reality is proposed. Methods A dual-pattern marker has been attached to the gamma probe, which combines chessboard vertices and circular dots for higher detection accuracy. Both patterns are detected simultaneously based on blob detection and the pixel intensity-based vertices detector and used to estimate the pose of the probe. Temporal information is incorporated into the framework to reduce tracking failure. Furthermore, we utilized the 3D point cloud generated from structure from motion to find the intersection between the probe axis and the tissue surface. When presented as an augmented image, this can provide visual feedback to the surgeons. Results The method has been validated with ground truth probe pose data generated using the OptiTrack system. When detecting the orientation of the pose using circular dots and chessboard dots alone, the mean error obtained is $$0.05^{\circ }$$ 0 . 05 ∘ and $$0.06^{\circ }$$ 0 . 06 ∘ , respectively. As for the translation, the mean error for each pattern is 1.78 mm and 1.81 mm. The detection limits for pitch, roll and yaw are $$360^{\circ }, 360^{\circ }$$ 360 ∘ , 360 ∘ and $$8^{\circ }$$ 8 ∘ –$$82^{\circ }\cup 188^{\circ }$$ 82 ∘ ∪ 188 ∘ –$$352^{\circ }$$ 352 ∘ . Conclusion The performance evaluation results show that this dual-pattern marker can provide high detection rates, as well as more accurate pose estimation and a larger workspace than the previously proposed hybrid markers. The augmented reality will be used to provide visual feedback to the surgeons on the location of the affected lymph nodes or tumor.

Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early stage, and at clinically relevant stages such as advanced stage and terminal stage with in vivo 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) and 67Ga-citrate single photon emission computed tomography (SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with 18F-Fluorine (F-18) and 67Ga-Gallium isotopes in the selection of infiltrated lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report in vivo detection of the Cerenkov light emission of 67Ga. CLI with 67Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery, has implications for tissue pathology processing and it could direct therapy. The results with 67Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.

Dense depth estimation and 3D reconstruction of a surgical scene are crucial steps in computer assisted surgery. Recent work has shown that depth estimation from a stereo image pair could be solved with convolutional neural networks. However, most recent depth estimation models were trained on datasets with per-pixel ground truth. Such data is especially rare for laparoscopic imaging, making it hard to apply supervised depth estimation to real surgical applications. To overcome this limitation, we propose SADepth, a new self-supervised depth estimation method based on Generative Adversarial Networks. It consists of an encoder-decoder generator and a discriminator to incorporate geometry constraints during training. Multi-scale outputs from the generator help to solve the local minima caused by the photometric reprojection loss, while the adversarial learning improves the framework generation quality. Extensive experiments on two public datasets show that SADepth outperforms recent state-of-the-art unsupervised methods by a large margin, and reduces the gap between supervised and unsupervised depth estimation in laparoscopic images.

Background Cerenkov Luminescence Imaging (CLI) is an emerging technology for intraoperative margin assessment. Previous research only evaluated radionuclide 18-Fluorine (18F); however, for future applications in prostate cancer, 68-Gallium (68Ga) seems more suitable, given its higher positron energy. Theoretical calculations predict that 68Ga should offer a higher signal-to-noise ratio than 18F; this is the first experimental confirmation. The aim of this study is to investigate the technical performance of CLI by comparing 68Ga to 18F. Results The linearity of the system, detection limit, spatial resolution, and uniformity were determined with the LightPath imaging system. All experiments were conducted with clinically relevant activity levels in vitro, using dedicated phantoms. For both radionuclides, a linear relationship between the activity concentration and detected light yield was observed (R2 = 0.99). 68Ga showed approximately 22 times more detectable Cerenkov signal compared to 18F. The detectable activity concentration after a 120 s exposure time and 2 × 2 binning of 18F was 23.7 kBq/mL and 1.2 kBq/mL for 68Ga. The spatial resolution was 1.31 mm for 18F and 1.40 mm for 68Ga. The coefficient of variance of the uniformity phantom was 0.07 for the central field of view. Conclusion 68Ga was superior over 18F in terms of light yield and minimal detection limit. However, as could be expected, the resolution was 0.1 mm less for 68Ga. Given the clinical constraints of an acquisition time less than 120 s and a spatial resolution 68Ga could be feasible.

Introduction In women undergoing breast-conserving surgery (BCS), 20–25% require a re-operation as a result of incomplete tumour resection. An intra-operative technique to assess tumour margins accurately would be a major advantage. A novel method for intraoperative margin assessment was developed by applying a thin flexible scintillating film to specimens—flexible autoradiography (FAR) imaging. A single-arm, multi-centre study was conducted to evaluate the feasibility of intraoperative [18F]FDG FAR for the assessment of tumour margins in BCS. Methods Eighty-eight patients with invasive breast cancer undergoing BCS received ≤ 300 MBq of [18F]FDG 60–180 min pre-operatively. Following surgical excision, intraoperative FAR imaging was performed using the LightPath® Imaging System. The first 16 patients were familiarisation patients; the remaining 72 patients were entered into the main study. FAR images were analysed post-operatively by three independent readers. Areas of increased signal intensity were marked, mean normalised radiances and tumour-to-tissue background (TBR) determined, agreement between histopathological margin status and FAR assessed and radiation dose to operating theatre staff measured. Subgroup analyses were performed for various covariates, with thresholds set based on ROC curves. Results Data analysis was performed on 66 patients. Intraoperative margin assessment using FAR was completed on 385 margins with 46.2% sensitivity, 81.7% specificity, 8.1% PPV, 97.7% NPV and an overall accuracy of 80.5%, detecting both invasive carcinoma and DCIS. A subgroup analysis based on [18F]FDG activity present at time of imaging revealed an increased sensitivity (71.4%), PPV (9.3%) and NPV (98.4%) in the high-activity cohort with mean tumour radiance and TBR of 126.7 ± 45.7 photons/s/cm2/sr/MBq and 2.1 ± 0.5, respectively. Staff radiation exposure was low (38.2 ± 38.1 µSv). Conclusion [18F]FDG FAR is a feasible and safe technique for intraoperative tumour margin assessment. Further improvements in diagnostic performance require optimising the method for scintillator positioning and/or the use of targeted radiopharmaceuticals. Trial registration: Identifier: NCT02666079. Date of registration: 28 January 2016. URL: https://clinicaltrials.gov/ct2/show/NCT02666079. ISRCTN registry: Reference: ISRCTN17778965. Date of registration: 11 February 2016. URL: http://www.isrctn.com/ISRCTN17778965.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation of lymphoma cells (n = 18 mice), and its advanced stage at seven days post-inoculation with in vivo [18F]FDG-PET and [18F]PET/MRI, and ex vivo by autoradiography and Cherenkov luminescence imaging (CLI). Of the early stage group, nine animals received intraperitoneal injections, and nine received intravenous [18F]FDG injections. The advanced stage group (n = 3) received intravenous FDG injections. In the early stage, using autoradiography we observed a marked accumulation in the mesentery after intraperitoneal FDG injection. Using other imaging methods and autoradiography, following the intravenous injection of FDG no accumulations were detected. At the advanced stage, tracer accumulation was clearly detected in mesenteric lymph nodes and in the peritoneum after intravenous administration using PET. We confirmed the results with immunohistochemistry. Our results in this model highlight the importance of local FDG administration during diagnostic imaging to precisely assess early peritoneal manifestations of other malignancies (colon, stomach, ovary). These findings also support the importance of applying topical therapies, in addition to systemic treatments in peritoneal cancer spread.

Arrays of interacting 2D nanomagnets display unprecedented electromagnetic properties via collective effects, demonstrated in artificial spin ices and magnonic crystals. Progress toward 3D magnetic metamaterials is hampered by two challenges: fabricating 3D structures near intrinsic magnetic length scales (sub-100 nm) and visualizing their magnetic configurations. Here, we fabricate and measure nanoscale magnetic gyroids, periodic chiral networks comprising nanowire-like struts forming three-connected vertices. Via block copolymer templating, we produce Ni75Fe25 single-gyroid and double-gyroid (an inversion pair of single-gyroids) nanostructures with a 42 nm unit cell and 11 nm diameter struts, comparable to the exchange length in Ni–Fe. We visualize their magnetization distributions via off-axis electron holography with nanometer spatial resolution and interpret the patterns using finite-element micromagnetic simulations. Our results suggest an intricate, frustrated remanent state which is ferromagnetic but without a unique equilibrium configuration, opening new possibilities for collective phenomena in magnetism, including 3D magnonic crystals and unconventional computing.

In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by 18F-FDG. Its high-resolution and small size imaging equipment make CLI a promising technology for intraoperative margin assessment. A first-in-human study was conducted to evaluate the feasibility of 18F-FDG CLI for intraoperative assessment of tumor margins in BCS. Methods: Twenty-two patients with invasive breast cancer received 18F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased 99mTc-nanocolloid activity of 150 MBq to facilitate nodal detection against the g-probe background signal (cross-talk) from 18F-FDG. The cross-talk and 99mTc dose required was evaluated in 2 lead-in studies. Immediately after excision, specimens were imaged intraoperatively in an investigational CLI system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 patients were included in the analysis dataset. Cerenkov luminescence images from incised BCS specimens were analyzed postoperatively by 2 surgeons blinded to the histopathology results, and mean radiance and margin distance were measured. The agreement between margin distance on CLI and histopathology was assessed. Radiation doses to staff were measured. Results: Ten of the 12 patients had an elevated tumor radiance on CLI. Mean radiance and tumor-to-background ratio were 560 6 160 photons/s/cm2/sr and 2.41 6 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (k 5 0.81 and 0.912, respectively). Sentinel lymph nodes were successfully detected in all patients. The radiation dose to staff was low; surgeons received a mean dose of 34 6 15 mSv per procedure. Conclusion: Intraoperative 18F-FDG CLI is a promising, low-risk technique for intraoperative assessment of tumor margins in BCS. A randomized controlled trial will evaluate the impact of this technique on reexcision rates.

IPv6 Routing Protocol for Low Power and Lossy Networks (RPL) proposed by Internet Engineering Task Force (IETF) has been adopted to suit Internet of Things (IoT) requirements. However, both the storing and non-storing modes of operation for RPL brings about certain limitations. In case of storing mode of RPL, if an intermediate node along the routing path overflows, new nodes become unreachable whereas, for the non-storing mode of RPL, the entire routing topology is only saved at the root node resulting in increased congestion near the root. Therefore, in this paper, we propose a low overhead Adaptive RPL (ARPL) algorithm which allows flexibility between storing and non-storing modes of operation. Here, the benefits of both the operating modes of RPL are utilized to avoid additional control message exchange, thereby making network resource-aware. We also observe that ARPL performs better than one state-of-the-art competitor in terms of storage and memory overflow by allowing the said flexibility of switching modes. Finally, we simulate ARPL using Cooja in Contiki operating system to evaluate the performance of ARPL. The simulation results show that ARPL achieves higher packet delivery ratio (PDR) in downward communication (e.g. query mode) while keeping convergence time same. It also shows that even in the mixed mode more than 90% nodes are operating in storing mode which improves Point to Point (P2P) communication with reduced traffic near the root thus allowing nodes to save energy.

Autoradiography potentially offers high molecular sensitivity and spatial resolution for tumor margin estimation. However, conventional autoradiography requires sectioning the sample which is destructive and labor-intensive. Here we describe a novel autoradiography technique that uses a flexible ultra-thin scintillator which conforms to the sample surface. Imaging with the flexible scintillator enables direct, high-resolution and high-sensitivity imaging of beta particle emissions from targeted radiotracers. The technique has the potential to identify positive tumor margins in fresh unsectioned samples during surgery, eliminating the processing time demands of conventional autoradiography. We demonstrate the feasibility of the flexible autoradiography approach to directly image the beta emissions from radiopharmaceuticals using lab experiments and GEANT-4 simulations to determine i) the specificity for 18 F compared to 99m Tc-labeled tracers ii) the sensitivity to detect signal from various depths within the tissue. We found that an image resolution of 1.5 mm was achievable with a scattering background and we estimate a minimum detectable activity concentration of 0.9 kBq/ml for 18 F. We show that the flexible autoradiography approach has high potential as a technique for molecular imaging of tumor margins using 18 F-FDG in a tumor xenograft mouse model imaged with a radiation-shielded EMCCD camera. Due to the advantage of conforming to the specimen, the flexible scintillator showed significantly better image quality in terms of tumor signal to whole-body background noise compared to rigid and optimally thick CaF 2 :Eu and BC400. The sensitivity of the technique means it is suitable for clinical translation.

We present a novel tunnel magnetoresistance (TMR) scanning microscope set-up capable of quantitatively imaging the magnetic stray field patterns of micron-sized elements in 3D. By incorporating an Anderson loop measurement circuit for impedance matching, we are able to detect magnetoresistance changes of as little as 0.006%/Oe. By 3D rastering a mounted TMR sensor over our magnetic barcodes, we are able to characterize the complex domain structures by displaying the real component, the amplitude and the phase of the sensor's impedance. The modular design, incorporating a TMR sensor with an optical microscope, renders this set-up a versatile platform for studying and imaging immobilised magnetic carriers and barcodes currently employed in biosensor platforms, magnetotactic bacteria and other complex magnetic domain structures of micron-sized entities. The quantitative nature of the instrument and its ability to produce vector maps of magnetic stray fields has the potential to provide significant advantages over other commonly used scanning magnetometry techniques.

We present a polarised neutron reflectivity (PNR) study of magnetic/non-magnetic (CoNiCu/Cu) thin films grown by single bath electrodeposition. We find that the composition is neither homogeneous with time, nor consistent with bulk values. Instead an initial, non-magnetic copper rich layer is formed, around 2 nm thick. This layer is formed by the deposition of the dilute, but rapidly diffusing, Cu2+ ions near the electrode surface at the start of growth, before the region is depleted and the deposition becomes mass transport limited. After the region has been depleted, by growth etc., this layer does not form and thus may be prevented by growing a copper buffer layer immediately preceding the magnetic layer growth. As has been previously found, cobalt deposits anomalously compared to nickel, and even inhibits Ni deposition in thin films. The layer magnetisation and average neutron scattering length are fitted independently but both depend upon the alloy composition. Thus these parameters can be used to check for model self-consistency, increasing confidence in the derived composition.

SU8 microcarriers containing magnetic thin film (40 nm cobalt) elements were fabricated by photolithography and thermal evaporation, and included a gold coating on the base. The microcarriers, which can be encoded with a magnetic barcode for later identification in a multiplexed suspension assay, now possess two distinct surfaces for further chemical derivitization. This allows us to attach different bio-molecules to each side, which we suggest, could be used to add a positive control to typical hybridization assays as a test for binding conditions, thus giving confidence against false negative events. As a proof-of-concept we developed a chemical pathway to attach 5',6'-tetramethyl rhodamine onto the gold coated side via the growth of a mixed self-assembled monolayer (characterized by Electrochemical Quartz Crystal Microbalance measurements), while also attaching fluorescein to the SU8 side after first adding a homo-bifunctional spacer to the native surface epoxide groups. Fluorescence microscopy was used to verify the success of this strategy and the feasibility of using PicoGreen as a post-hybridization reporter was studied.

In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by

Microarrays and suspension-based assay technologies have attracted significant interest over the past decade with applications ranging from medical diagnostics to high throughput molecular biology. The throughput and sensitivity of a microarray will always be limited by the array density and slow reaction kinetics. Suspension (or bead) based technologies offer a conceptually different approach, improving detection by substituting a fixed plane of operation with millions of microcarriers. However, these technologies are currently limited by the number of unique labels that can be generated in order to identify the molecular probes on the surface. We have proposed a novel suspension-based technology that utilizes patterned magnetic films for the purpose of generating a writable label. The microcarriers consist of an SU-8 substrate that can be functionalized with various chemical or biological probes and magnetic elements, which are individually addressable by a magnetic sensor. The magnetization of each element is aligned in one of two stable directions, thereby acting as a magnetic bit. In order to detect the stray field and identify the magnetic labels, we have developed a microfluidic device with an integrated tunneling magnetoresistive (TMR) sensor, sourced from Micro Magnetics Inc. We present the TMR embedding architecture as well as detection results demonstrating the feasibility of magnetic labeling for lab-on-a-chip applications.

The magnetotactic bacterium Magnetospirillum sp. has been cultured and the properties of its endogenous magnetic nanoparticles characterized. Electron-microscopic analyses indicate that the endogenous magnetite nanoparticles in Magnetospirillum sp. are coated with a 3–4 nm thick transparent shell, forming a magnetosome. These magnetite nanoparticles had diameters of 50.9±13.3 nm, in good agreement with the diameter of 40.6±1.2 nm extracted from magnetometry. Each Magnetospirillum sp. bacterium contained chains of 5–25 magnetosomes. Superconducting quantum interference device magnetometry results indicate that the extrinsic superparamagnetic response of the bacterial solution at room temperature can be attributed to the reversal of the magnetization by physical rotation of the nanoparticles. The intrinsic blocking temperature of a sample of freeze-dried bacteria was estimated to be 282±13 K. A tunnelling magneto resistance sensor was used to detect the stray fields of endogenous magnetic nanoparticles in static and quasi-dynamic modes. Based on the tunnelling magneto resistance sensor results, the magnetic moment per bacterium was estimated to be approximately 2.6×10 −13 emu. The feasibility of this detection method either as a mass-coverage device or as part of an integrated microfluidic circuit for detection and sorting of magnetosome-containing cells was demonstrated.

International audience; We describe proof-of-principle experiments and theory that demonstrate a new method of performing multiplexed biological assays by using microscopic tags which carry multi-bit magnetic codes to label probe biomolecules. It is demonstrated that these " micro-barcode tags " can be encoded, transported using micro-fluidics and are compatible with surface chemistry. We also present simulations and experimental results which suggest the feasibility of decoding the micro-barcode tags using magnetoresistive sensors. Together, these results demonstrate substantial progress towards meeting the critical requirements of a magnetically encoded, high-throughput and portable biological assay platform. We also show that an extension of our technology could be potentially used to label libraries consisting of ~10 4 distinct probe molecules, and could therefore have a strong impact on mainstream medical diagnostics.

S S53 Introduction: Oncoplastic techniques are increasingly used in breast conserving surgery for better aesthetic outcome following breast cancer treatment without compromising oncological principles. This modified periareolar mammaplasty (MPM) gives excellent access for wide local excision, avoids scar on the breast mound and also gives a pleasing aesthetic outcome. We have critically evaluated our technique including oncological and aesthetic outcomes over a 14-month period. Methods: Details of patientswho underwentMPMbetweenOct 2013 and Dec 2014 were retrieved from our prospectively collected breast cancer operations database. Patient’s operative details including thedurationof operation, specimenweight, histopathology data, adjuvant therapy details and follow-up visits were updated. Medical photography was reviewed for all patients. Results: 25 women underwent MPM. The median age was 60 yrs (range 37e82). The median specimen weight was 34g (range 17e76). Along with breast cancer surgery, most of them had axillary staging according to standard practice. Two patients had re-excision of margins and one patient underwent completion skin sparing mastectomy for involved margins. Postoperative recovery and wound healing were uneventful except one patient had infection of axillary wound. 23 patients underwent radiotherapy to the breast remnant. Medical photography shows excellent aesthetic outcomes. Conclusion: MPM is a type of therapeutic mammaplasty which is easy to learn and reproduce, and a useful adjunct to oncoplastic breast conserving surgery. http://dx.doi.org/10.1016/j.ejso.2015.03.131 P094. Clinical feasibility of Cerenkov Luminescence Imaging (CLI) for intraoperative assessment of tumour excision margins and sentinel lymph node metastases in breast-conserving surgery Maarten Ruben Grootendorst, Ashutosh Kothari, Massimiliano Cariati, Hisham Hamed, Michael Douek, Tibor Kovacs, Gary Cook, Sarah Allen, Chris Sibley-Allen, Alan Britten, Amit Pawa, Fiona Nimmo, Kunal Vyas, David Tuch, Sarah Pinder, Arnie Purushotham, on behalf of the Cerenkov Luminescence Imaging Study Group 1 Department of Research Oncology, King’s College London, London, UK Department of Breast Surgery, Guy’s and St Thomas’ NHS Foundation Trust, London, UK 3 PET Imaging Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Department of Nuclear Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Medical Physics Department, St George’s Hospital, London, UK Anaesthetic Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Day Surgery Unit, Guy’s and St Thomas’ NHS Foundation Trust, London, UK 8 Sagentia, Cambridge, UK Lightpoint Medical Ltd., Rickmansworth, UK Introduction: Cerenkov Luminescence Imaging (CLI) is a molecular imaging technique that detects light emitted by Positron Emission Tomography (PET) radiopharmaceuticals. This first-in-woman study evaluates F-FDG CLI for intraoperative assessment of tumour margins and sentinel lymph node (SLN) metastases with a view to reducing re-excision rates. Methods: To date 8 of 30 patients have been recruited (REC reference 14/WM/0050). Patients received 5 MBq/kg F-FDG 1e2 hours prior to surgery. Tc dose was increased to 150 MBq to facilitate SLN detection against the gamma-probe background signal (cross-talk) from F-FDG. The cross-talk was evaluated in a separate lead-in study of n 1⁄4 20 patients. Tumour specimens and SLNs were imaged with a CLI imager (Lightpoint Medical Ltd, UK) intraoperatively immediately after excision. Normalised decay-corrected radiance (ph/s/cm/str/MBq) was calculated for each ROI. Radiation doses to all staff were measured. Results: Elevated radiance was identified in the primary tumour (26.7 ROI SD 3.2), and the only metastatic (8mm) SLN (42.1 ROI SD 9.1) compared with negative SLNs (16.2 SD 12.5). The mean F-FDG cross-talk in the lead-in study was 348 cps and 357 cps in left and right axilla, respectively. SLN detection was successful in all patients undergoing CLI despite substantial F-FDG cross-talk. Table Staff radiation doses Staff Average dose per Maximum procedure (mSv) dose (mSv) Surgeon 28.6 64 Anaesthetist 8.6 15 Anaesthetist assistant 6.4 11 Scrub nurse 1.8 5 Recovery nurse 6.6 17 Conclusions: Intraoperative F-FDG CLI is a feasible and low risk procedure. Despite significant cross-talk, SLN biopsy can be performed successfully using 150 MBq Tc and blue dye. http://dx.doi.org/10.1016/j.ejso.2015.03.132 P095. Chemotherapy trends in early breast cancer in the under 55s in 2014 Caroline Strachan, Rajiv Dave, Sue Hartup, Nisha Sharma, Tom Hughes, Kieran Horgan The Leeds Breast Unit, St James University Hospital, Leeds, West Yorkshire, UK Neoadjuvant chemotherapy (NACT) is increasingly employed for early breast cancer in younger women with the potential benefit over adjuvant treatment (ACT) of conserving the breast and monitoring response. With wider ranging indications for NACT, is the use of ACT in the under 55s diminishing? Methodology: Clinico-pathological characteristics of patients under 55 undergoing chemotherapy in our unit over the last year were analysed, to review selection criteria for ACT in this age group. Results: 195 patients under 55 were diagnosed with breast cancers in 2014. 37 under 55 received NACT. 122 Patients under 55 consulted an oncologist for consideration of ACT and 54 patients (60%) received it. 68 patients did not receive ACT, due to personal choice or “adjuvantonline” / oncologist opinion not being persuasive. ACT in the 54 patients was preceded by breast conserving surgery (BCT) in 28 patients, and by mastectomies (Mx) in 26. Of the 26 who had Mx, 12 were considered obligate mastectomy candidates regardless of potential NACT response. 11 chose to have Mx, with 8 of those 11 being offered NACT. In 3 patients, Mx was performed for widespread DCIS and chemotherapy was not anticipated pre-operatively. Of the 28 patients who underwent BCT, NACT was not discussed as they were already conservable and MDT saw no benefit. Conclusions: The majority of younger women with early breast cancer treated with chemotherapy still receive it as an adjuvant treatment. 52% of women receiving adjuvant therapy do so as they are considered conservable without discussing primary systemic therapy, whereas 22%were deemed not conservable evenwithNACT.Adjuvant administration therefore remains the mainstay of systemic chemotherapy in this cohort of women. http://dx.doi.org/10.1016/j.ejso.2015.03.133

Microarrays and suspension-based assay technologies have attracted significant interest over the past decade with applications ranging from medical diagnostics to high throughput molecular biology. The throughput and sensitivity of a microarray will always be limited by the array density and slow reaction kinetics. Suspension (or bead) based technologies offer a conceptually different approach, improving detection by substituting a fixed plane of operation with many individually distinguishable microcarriers. In addition to all the features of a suspension based assay technology, our technology offers a rewritable label. This has the potential to be truly revolutionary by opening up the possibility of generating, on chip, extensive labelled molecular libraries. We unveil our latest SU-8 microcarrier design with embedded magnetic films that can be utilized for both magnetic and optical labelling. The novel design significantly simplifies fabrication and additionally incorporates a gold cap to provide a dual surface, bi-functional architecture. The microcarriers are fabricated using deep-ultraviolet lithography techniques and metallic thin film growth by evaporation. The bi-functional properties of the microcarriers will allow us to use each microcarrier as its own positive control thereby increasing the reliability of our technology. Here we present details of the design, fabrication, magnetic detection and functionalization of these microcarriers.

Microarrays and suspension-based technologies have attracted significant interest over the past decade with applications in medical diagnostics and biochemical multiplexed assays. However, the throughput of microarrays will always be limited by the array density and the slow kinetics, while the suspension (or bead)-based technologies are currently limited by the number of distinct codes the beads can carry. A novel digital magnetic tagging technology based on magnetic tags that can be used as encoded microcarriers for biomolecular probes, is presented here. The highly disruptive platform technology can provide a very large number of unique codes, enabling a high degree of multiplexing. The design principles of a novel magnetic laboratory-on-a-chip device comprising microfluidic channels with embedded magnetic tunneling magnetoresistive sensors are also discussed.

The challenge in delineating the boundary between cancerous and healthy tissue during cancer resection surgeries can be addressed with the use of intraoperative probes to detect cancer cells labelled with radiotracers to facilitate excision. In this study, deep learning algorithms for background gamma ray signal rejection were explored for an intraoperative probe utilising CMOS monolithic active pixel sensors optimised towards the detection of internal conversion electrons from 99mTc. Two methods utilising convolutional neural networks (CNNs) were explored for beta-gamma discrimination: 1) classification of event clusters isolated from the sensor array outputs (SAOs) from the probe and 2) semantic segmentation of event clusters within an acquisition frame of an SAO. The feasibility of the methods in this study was explored with several radionuclides including 14C, 57Co and 99mTc. Overall, the classification deep network is able to achieve an improved area under the curve (AUC) of the receiver operating characteristic (ROC), giving 0.93 for 14C beta and 99mTc gamma clusters, compared to 0.88 for a more conventional feature-based discriminator. Further optimisation of the lower left region of the ROC by using a customised AUC loss function during training led to an improvement of 33% in sensitivity at low false positive rates compared to the conventional method. The segmentation deep network is able to achieve a mean dice score of 0.93. Through the direct comparison of all methods, the classification method was found to have a better performance in terms of the AUC.