Cerenkov Luminescence Imaging in Prostate Cancer: Not the Only Light That Shines.

Cerenkov luminescence imaging (CLI) is a novel imaging technology that might have the ability to assess surgical margins intraoperatively during prostatectomy using 68Ga-prostate-specific membrane antigen (68Ga-PSMA-11). This study evaluated the accuracy of CLI compared with histopathology and, as an exploratory objective, investigated the characteristics of the identified chemiluminescence signal. Methods: After intravenous injection of a mean 68Ga-PSMA-11 activity of 69 MBq intraoperatively, all excised specimens were imaged with CLI. Areas of increased signal were marked for histopathologic comparison and scored for the likelihood of being a positive surgical margin (PSM) using a 5-point Likert scale. In addition, the chemiluminescence signal was investigated in 3 radioactive and 3 nonradioactive specimens using CLI. Results: In 15 patients, the agreement between CLI and histopathology was 60%; this improved to 83% when including close surgical margins (≤1 mm). In 6 hot spots, 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 8 patients. This chemiluminescence signal was also observed in nonradioactive prostate specimens, with a half-life of 48 ± 11 min. The chemiluminescence hampered the visual interpretation of 4 PSMs at the base. Conclusion: CLI was 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.

Intraoperative [18F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study.

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 .

Visualizing Magnetic Structure in 3D Nanoscale Ni-Fe Gyroid Networks.

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.

68Ga-PSMA Cerenkov luminescence imaging in primary prostate cancer: first-in-man series.

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 < 0.1 mm from the excision margin. 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.

The Scanning TMR Microscope for Biosensor Applications.

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.

Magnetically labelled gold and epoxy bi-functional microcarriers for suspension based bioassay technologies.

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.