Position- and posture-dependent vascular imaging-a scoping review.

OBJECTIVES: Position- and posture-dependent deformation of the vascular system is a relatively unexplored field. The goal of this scoping review was to create an overview of existing vascular imaging modalities in different body positions and postures and address the subsequent changes in vascular anatomy. METHODS: Scopus, Medline, and Cochrane were searched for literature published between January 1, 2000, and June 30, 2022, incorporating the following categories: image modality, anatomy, orientation, and outcomes. RESULTS: Out of 2446 screened articles, we included 108. The majority of papers used ultrasound (US, n = 74) in different body positions and postures with diameter and cross-sectional area (CSA) as outcome measures. Magnetic resonance imaging (n = 22) and computed tomography (n = 8) were less frequently used but allowed for investigation of other geometrical measures such as vessel curvature and length. The venous system proved more sensitive to postural changes than the arterial system, which was seen as increasing diameters of veins below the level of the heart when going from supine to prone to standing positions, and vice versa. CONCLUSIONS: The influence of body positions and postures on vasculature was predominantly explored with US for vessel diameter and CSA. Posture-induced deformation and additional geometrical features that may be of interest for the (endovascular) treatment of vascular pathologies have been limitedly reported, such as length and curvature of an atherosclerotic popliteal artery during bending of the knee after stent placement. The most important clinical implications of positional changes are found in diagnosis, surgical planning, and follow-up after stent placement. CLINICAL RELEVANCE STATEMENT: This scoping review presents the current state and opportunities of position- and posture-dependent imaging of vascular structures using various imaging modalities that are relevant in the fields of clinical diagnosis, surgical planning, and follow-up after stent placement. KEY POINTS: • The influence of body positions and postures on the vasculature was predominantly investigated with US for vessel diameter and cross-sectional area. • Research into geometrical deformation, such as vessel length and curvature adaptation, that may be of interest for the (endovascular) treatment of vascular pathologies is limited in different positions and postures. • The most important clinical implications of postural changes are found in diagnosis, surgical planning, and follow-up after stent placement.

Radiofrequency localization of nonpalpable breast cancer in a multicentre prospective cohort study: feasibility, clinical acceptability, and safety.

PURPOSE: In breast conserving surgery, accurate lesion localization is essential for obtaining adequate surgical margins. Preoperative wire localization (WL) and radioactive seed localization (RSL) are widely accepted methods to guide surgical excision of nonpalpable breast lesions but are limited by logistical challenges, migration issues, and legislative complexities. Radiofrequency identification (RFID) technology may offer a viable alternative. The purpose of this study was to evaluate the feasibility, clinical acceptability, and safety of RFID surgical guidance for localization of nonpalpable breast cancer. METHODS: In a prospective multicentre cohort study, the first 100 RFID localization procedures were included. The primary outcome was the percentage of clear resection margins and re-excision rate. Secondary outcomes included procedure details, user experience, learningcurve, and adverse events. RESULTS: Between April 2019 and May 2021, 100 women underwent RFID guided breast conserving surgery. Clear resection margins were obtained in 89 out of 96 included patients (92.7%), re-excision was indicated in three patients (3.1%). Radiologists reported difficulties with the placement of the RFID tag, partially related to the relatively large needle-applicator (12-gauge). This led to the premature termination of the study in the hospital using RSL as regular care. The radiologist experience was improved after a manufacturer modification of the needle-applicator. Surgical localization involved a low learning curve. Adverse events (n = 33) included dislocation of the marker during insertion (8%) and hematomas (9%). The majority of adverse events (85%) occurred using the first-generation needle-applicator. CONCLUSION: RFID technology is a potential alternative for non-radioactive and non-wire localization of nonpalpable breast lesions.

Modelling of Dynamic Behaviour in Magnetic Nanoparticles.

The efficient development and utilisation of magnetic nanoparticles (MNPs) for applications in enhanced biosensing relies on the use of magnetisation dynamics, which are primarily governed by the time-dependent motion of the magnetisation due to externally applied magnetic fields. An accurate description of the physics involved is complex and not yet fully understood, especially in the frequency range where Néel and Brownian relaxation processes compete. However, even though it is well known that non-zero, non-static local fields significantly influence these magnetisation dynamics, the modelling of magnetic dynamics for MNPs often uses zero-field dynamics or a static Langevin approach. In this paper, we developed an approximation to model and evaluate its performance for MNPs exposed to a magnetic field with varying amplitude and frequency. This model was initially developed to predict superparamagnetic nanoparticle behaviour in differential magnetometry applications but it can also be applied to similar techniques such as magnetic particle imaging and frequency mixing. Our model was based upon the Fokker-Planck equations for the two relaxation mechanisms. The equations were solved through numerical approximation and they were then combined, while taking into account the particle size distribution and the respective anisotropy distribution. Our model was evaluated for Synomag®-D70, Synomag®-D50 and SHP-15, which resulted in an overall good agreement between measurement and simulation.

Nationwide registry study on trends in localization techniques and reoperation rates in non-palpable ductal carcinoma in situ and invasive breast cancer.

BACKGROUND: There is a transition from wire-guided localization (WGL) of non-palpable breast cancer to other localization techniques. Multiple prospective studies have sought to establish superior clinical outcomes for radioactive-seed localization (RSL), but consistent and congruent evidence is missing. METHODS: In this study, female patients with breast cancer operated with breast-conserving surgery after tumour localization of a non-palpable breast cancer or ductal carcinoma in situ (DCIS) were included. The cohort was identified from the nationwide Netherlands Breast Cancer Audit conducted between 2013 and 2018. Trends in localization techniques were analysed. Univariable and multivariable analyses were performed to assess the association between the localization technique and the probability of a reoperation. RESULTS: A total of 28 370 patients were included in the study cohort. The use of RSL increased from 15.7 to 61.1 per cent during the study years, while WGL decreased from 75.4 to 31.6 per cent. The localization technique used (RSL versus WGL) was not significantly associated with the odds of a reoperation, regardless of whether the lesion was DCIS (odds ratio 0.96 (95 per cent c.i. 0.89 to 1.03; P = 0.281)) or invasive breast cancer (OR 1.02 (95 per cent c.i. 0.96 to 1.10; P = 0.518)). CONCLUSION: RSL is rapidly replacing WGL as the preoperative localization technique in breast surgery. This large nationwide registry study found no association between the type of localization technique and the odds of having a reoperation, thus confirming the results of previous prospective cohort studies.

Comparing the signal enhancement of a gadolinium based and an iron-oxide based contrast agent in low-field MRI.

Recently, there has been a renewed interest in low-field MRI. Contrast agents (CA) in MRI have magnetic behavior dependent on magnetic field strength. Therefore, the optimal contrast agent for low-field MRI might be different from what is used at higher fields. Ultra-small superparamagnetic iron-oxides (USPIOs), commonly used as negative CA, might also be used for generating positive contrast in low-field MRI. The purpose of this study was to determine whether an USPIO or a gadolinium based contrast agent is more appropriate at low field strengths. Relaxivity values of ferumoxytol (USPIO) and gadoterate (gadolinium based) were used in this research to simulate normalized signal intensity (SI) curves within a concentration range of 0-15 mM. Simulations were experimentally validated on a 0.25T MRI scanner. Simulations and experiments were performed using spin echo (SE), spoiled gradient echo (SGE), and balanced steady-state free precession (bSSFP) sequences. Maximum achievable SIs were assessed for both CAs in a range of concentrations on all sequences. Simulations at 0.25T showed a peak in SIs at low concentrations ferumoxytol versus a wide top at higher concentrations for gadoterate in SE and SGE. Experiments agreed well with the simulations in SE and SGE, but less in the bSSFP sequence due to overestimated relaxivities in simulations. At low magnetic field strengths, ferumoxytol generates similar signal enhancement at lower concentrations than gadoterate.

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [99mTc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.

Mono, bi- and tri-exponential diffusion MRI modelling for renal solid masses and comparison with histopathological findings.

PURPOSE: To compare diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and tri-exponential models of the diffusion magnetic resonance imaging (MRI) signal for the characterization of renal lesions in relationship to histopathological findings. METHODS: Sixteen patients planned to undergo nephrectomy for kidney tumour were scanned before surgery at 3 T magnetic resonance imaging (MRI), with T2-weighted imaging, DTI and diffusion weighted imaging (DWI) using ten b-values. DTI parameters (mean diffusivity [MD] and fractional anisotropy [FA]) were obtained by iterative weighted linear least squared fitting of the DTI data and bi-, and tri-exponential fit parameters (Dbi, fstar,and Dtri, ffast,finterm) using a nonlinear fit of the multiple b-value DWI data. Average parameters were calculated for regions of interest, selecting the lesions and healthy kidney tissue. Tumour type and specificities were determined after surgery by histological examination. Mean parameter values of healthy tissue and solid lesions were compared using a Wilcoxon-signed ranked test and MANOVA. RESULTS: Thirteen solid lesions (nine clear cell carcinomas, two papillary renal cell carcinoma, one haemangioma and one oncocytoma) and four cysts were included. The mean MD of solid lesions are significantly (p < 0.05) lower than healthy cortex and medulla, (1.94 ± 0.32*10- 3 mm2/s versus 2.16 ± 0.12*10- 3 mm2/s and 2.21 ± 0.14*10- 3 mm2/s, respectively) whereas ffast is significantly higher (7.30 ± 3.29% versus 4.14 ± 1.92% and 4.57 ± 1.74%) and finterm is significantly lower (18.7 ± 5.02% versus 28.8 ± 5.09% and 26.4 ± 6.65%). Diffusion coefficients were high (≥2.0*10- 3 mm2/s for MD, 1.90*10- 3 mm2/s for Dbi and 1.6*10- 3 mm2/s for Dtri) in cc-RCCs with cystic structures and/or haemorrhaging and low (≤1.80*10- 3 mm2/s for MD, 1.40*10- 3 mm2/s for Dbi and 1.05*10- 3 mm2/s for Dtri) in tumours with necrosis or sarcomatoid differentiation. CONCLUSION: Parameters derived from a two- or three-component fit of the diffusion signal are sensitive to histopathological features of kidney lesions.

Metal artefacts severely hamper magnetic resonance imaging of the rotator cuff tendons after rotator cuff repair with titanium suture anchors.

BACKGROUND: The rate of retear after rotator cuff surgery is 17%. Magnetic resonance imaging (MRI) scans are used for confirmative diagnosis of retear. However, because of the presence of titanium suture anchors, metal artefacts on the MRI are common. The present study evaluated the diagnostic value of MRI after rotator cuff tendon surgery with respect to assessing the integrity as well as the degeneration and atrophy of the rotator cuff tendons when titanium anchors are in place. METHODS: Twenty patients who underwent revision surgery of the rotator cuff as a result of a clinically suspected retear between 2013 and 2015 were included. The MRI scans of these patients were retrospectively analyzed by four specialized shoulder surgeons and compared with intra-operative findings (gold standard). Sensitivity and interobserver agreement among the surgeons in assessing retears as well as the Goutallier and Warner classification were examined. RESULTS: In 36% (range 15% to 50%) of the pre-operative MRI scans, the observers could not review the rotator cuff tendons. When the rotator cuff tendons were assessable, a diagnostic accuracy with a mean sensitivity of 0.84 (0.70 to 1.0) across the surgeons was found, with poor interobserver agreement (kappa = 0.12). CONCLUSIONS: Metal artefacts prevented accurate diagnosis from MRI scans of rotator cuff retear in 36% of the patients studied.

Pulmonary surfactant protein SP-D opsonises carbon nanotubes and augments their phagocytosis and subsequent pro-inflammatory immune response.

Carbon nanotubes (CNTs) are increasingly being developed for use in biomedical applications, including drug delivery. One of the most promising applications under evaluation is in treating pulmonary diseases such as tuberculosis. Once inhaled or administered, the nanoparticles are likely to be recognised by innate immune molecules in the lungs such as hydrophilic pulmonary surfactant proteins. Here, we set out to examine the interaction between surfactant protein D (SP-D), a key lung pattern recognition molecule and CNTs, and possible downstream effects on the immune response via macrophages. We show here that a recombinant form of human SP-D (rhSP-D) bound to oxidised and carboxymethyl cellulose (CMC) coated CNTs via its C-type lectin domain and enhanced phagocytosis by U937 and THP-1 macrophages/monocytic cell lines, together with an increased pro-inflammatory response, suggesting that sequestration of SP-D by CNTs in the lungs can trigger an unwanted and damaging immune response. We also observed that functionalised CNTs, opsonised with rhSP-D, continued to activate complement via the classical pathway, suggesting that C1q, which is the recognition sub-component of the classical pathway, and SP-D have distinct pattern recognition sites on the CNTs. Consistent with our earlier reports, complement deposition on the rhSP-D opsonised CNTs led to dampening of the pro-inflammatory immune response by THP-1 macrophages, as evident from qPCR, cytokine array and NF-κB nuclear translocation analyses. This study highlights the importance of understanding the interplay between innate immune humoral factors including complement in devising nanoparticle based drug delivery strategies.

Intravoxel incoherent motion modeling in the kidneys: Comparison of mono-, bi-, and triexponential fit.

PURPOSE: To evaluate if a three-component model correctly describes the diffusion signal in the kidney and whether it can provide complementary anatomical or physiological information about the underlying tissue. MATERIALS AND METHODS: Ten healthy volunteers were examined at 3T, with T2 -weighted imaging, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM). Diffusion tensor parameters (mean diffusivity [MD] and fractional anisotropy [FA]) were obtained by iterative weighted linear least squares fitting of the DTI data and mono-, bi-, and triexponential fit parameters (D1 , D2 , D3 , ffast2 , ffast3 , and finterm ) using a nonlinear fit of the IVIM data. Average parameters were calculated for three regions of interest (ROIs) (cortex, medulla, and rest) and from fiber tractography. Goodness of fit was assessed with adjusted R2 ( Radj2) and the Shapiro-Wilk test was used to test residuals for normality. Maps of diffusion parameters were also visually compared. RESULTS: Fitting the diffusion signal was feasible for all models. The three-component model was best able to describe fast signal decay at low b values (b < 50), which was most apparent in Radj2 of the ROI containing high diffusion signals (ROIrest ), which was 0.42 ± 0.14, 0.61 ± 0.11, 0.77 ± 0.09, and 0.81 ± 0.08 for DTI, one-, two-, and three-component models, respectively, and in visual comparison of the fitted and measured S0 . None of the models showed significant differences (P > 0.05) between the diffusion constant of the medulla and cortex, whereas the ffast component of the two and three-component models were significantly different (P < 0.001). CONCLUSION: Triexponential fitting is feasible for the diffusion signal in the kidney, and provides additional information. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:228-239.

Phantom study quantifying the depth performance of a handheld magnetometer for sentinel lymph node biopsy.

PURPOSE: The use of a magnetic nanoparticle tracer and handheld magnetometer for sentinel lymph node biopsy (SLNB) was recently introduced to overcome drawbacks associated with the use of radioisotope tracers. Unlike the gamma probe, the used magnetometers are not only sensitive to the tracer, but also the diamagnetic human body. This potentially limits the performance of the magnetometer when used clinically. METHODS: A phantom, mimicking the magnetic and mechanical properties of the human axilla, was constructed. The depth performance of two current generation magnetometers was evaluated in this phantom. LN-phantoms with tracer uptake ranging from 5 to 500µg iron were placed at clinically relevant depths of 2.5, 4 and 5.5cm. Distance-response curves were obtained to quantify the depth performance of the probes. RESULTS: The depth performance of both probes was limited. In the absence of diamagnetic material and forces on the probe (ideal conditions) a LN-phantom with high uptake (500µg iron) could first be detected at 3.75cm distance. In the phantom, only superficially placed LNs (2.5cm) with high uptake (500µg iron) could be detected from the surface. The penetration depth was insufficient to detect LNs with lower uptake, or which were located deeper. CONCLUSION: The detection distance of the current generation magnetometers is limited, and does not meet the demands formulated by the European Association for Nuclear Medicine for successful transcutaneous SLN localization. Future clinical trials should evaluate whether the limited depth sensitivity is of influence to the clinical outcome of the SLNB procedure.

Complement Deposition on Nanoparticles Can Modulate Immune Responses by Macrophage, B and T Cells.

Nanoparticles are attractive drug delivery vehicles for targeted organ-specific as well as systemic therapy. However, their interaction with the immune system offers an intriguing challenge to the success of nanotherapeutics in vivo. Recently, we showed that pristine and derivatised carbon nanotubes (CNT) can activate complement mainly via the classical pathway leading to enhanced uptake by phagocytic cells, and transcriptional down-regulation of pro-inflammatory cytokines. Here, we report the interaction of complement-activating CC-CNT and RNA-CNT, and non-complement-activating gold-nickel (Au-Ni) nanowires with cell lines representing macrophage, B and T cells. Complement deposition considerably enhanced uptake of CNTs by immune cells known to overexpress complement receptors. Real-Time qPCR and multiplex array analyses showed complement-dependent down-regulation of TNF-α and IL-1ß and up-regulation of IL-12 by CMC- and RNA-CNTs, in addition to revealing IL-10 as a crucial regulator during nanoparticle-immune cell interaction. It appears that complement system can recognize molecular patterns differentially displayed by nanoparticles and thus, modulate subsequent processing of nanoparticles by antigen capturing and antigen presenting cells, which can shape innate and adaptive immune axes.

Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients.

PURPOSE: To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors. METHODS AND MATERIALS: For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT. RESULTS: The robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0-21.1) and 8.1% (95% CI; 4.9-11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing. CONCLUSIONS: The estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans.

Pre-operative sentinel lymph node localization in breast cancer with superparamagnetic iron oxide MRI: the SentiMAG Multicentre Trial imaging subprotocol.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) with a superparamagnetic iron oxide (SPIO) tracer was shown to be non-inferior to the standard combined technique in the SentiMAG Multicentre Trial. The MRI subprotocol of this trial aimed to develop a magnetic alternative for pre-operative lymphoscintigraphy (LS). We evaluated the feasibility of using MRI following the administration of magnetic tracer for pre-operative localization of sentinel lymph nodes (SLNs) and its potential for non-invasive identification of lymph node (LN) metastases. METHODS: Patients with breast cancer scheduled to undergo SLNB were recruited for pre-operative LS, single photon emission CT (SPECT)-CT and SPIO MRI. T1 weighted turbo spin echo and T2 weighted gradient echo sequences were used before and after interstitial injection of magnetic tracer into the breast. SLNs on MRI were defined as LNs with signal drop and direct lymphatic drainage from the injection site. LNs showing inhomogeneous SPIO uptake were classified as metastatic. During surgery, a handheld magnetometer was used for SLNB. Blue or radioactive nodes were also excised. The number of SLNs and MR assessment of metastatic involvement were compared with surgical and histological outcomes. RESULTS: 11 patients were recruited. SPIO MRI successfully identified SLNs in 10 of 11 patients vs 11 of 11 patients with LS/SPECT-CT. One patient had metastatic involvement of four LNs, and this was identified in one node on pre-operative MRI. CONCLUSION: SPIO MRI is a feasible technique for pre-operative localization of SLNs and, in combination with intraoperative use of a handheld magnetometer, provides an entirely radioisotope-free technique for SLNB. Further research is needed for the evaluation of MRI characterization of LN involvement using subcutaneous injection of magnetic tracer. ADVANCES IN KNOWLEDGE: This study is the first to demonstrate that an interstitially administered magnetic tracer can be used both for pre-operative imaging and intraoperative SLNB, with equal performance to imaging and localization with radioisotopes.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. FROM THE CLINICAL EDITOR: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.

How does spreading depression spread? Physiology and modeling.

Spreading depression (SD) is a wave phenomenon in gray matter tissue. Locally, it is characterized by massive redistribution of ions across cell membranes. As a consequence, there is sustained membrane depolarization and tissue polarization that depress any normal electrical activity. Despite these dramatic events, SD remains difficult to observe in humans noninvasively, which, for long, has slowed advances in this field. The growing appreciation of its clinical importance in migraine and stroke is therefore consistent with an increasing need for computational methods that tackle the complexity of the problem at multiple levels. In this review, we focus on mathematical tools to investigate the question of spread and its two complementary aspects: What are the physiological mechanisms and what is the spatial extent of SD in the cortex? This review discusses two types of models used to study these two questions, namely, Hodgkin-Huxley type and generic activator-inhibitor models, and the recent advances in techniques to link them.

Optimising magnetic sentinel lymph node biopsy in an in vivo porcine model.

The magnetic technique for sentinel lymph node biopsy (SLNB) has been evaluated in several clinical trials. An in vivo porcine model was developed to optimise the magnetic technique by evaluating the effect of differing volume, concentration and time of injection of magnetic tracer. A total of 60 sentinel node procedures were undertaken. There was a significant correlation between magnetometer counts and iron content of excised sentinel lymph nodes (SLNs) (r=0.82; P<0.001). Total number of SLNs increased with increasing volumes of magnetic tracer (P<0.001). Transcutaneous magnetometer counts increased with increasing time from injection of magnetic tracer (P<0.0001), plateauing within 60min. Increasing concentration resulted in higher iron content of SLNs (P=0.006). Increasing magnetic tracer volume and injecting prior to surgery improve transcutaneous 'hotspot' identification but very high volumes, increase the number of nodes excised. FROM THE CLINICAL EDITOR: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging of breast cancer patients. Although the current gold standard technique is the combined injection of technetium-labelled nanocolloid and blue dye into the breast, the magnetic technique, using superparamagnetic carboxydextran-coated iron oxide (SPIO), has also been demonstrated as a feasible alternative. In this article, the authors set up to study factors in order to optimize the magnetic tracers.

Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model.

INTRODUCTION: Breast cancer staging with sentinel lymph node biopsy relies on the use of radioisotopes, which limits the availability of the procedure worldwide. The use of a magnetic nanoparticle tracer and a handheld magnetometer provides a radiation-free alternative, which was recently evaluated in two clinical trials. The hydrodynamic particle size of the used magnetic tracer differs substantially from the radioisotope tracer and could therefore benefit from optimization. The aim of this study was to assess the performance of three different-sized magnetic nanoparticle tracers for sentinel lymph node biopsy within an in vivo porcine model. MATERIALS AND METHODS: Sentinel lymph node biopsy was performed within a validated porcine model using three magnetic nanoparticle tracers, approved for use in humans (ferumoxytol, with hydrodynamic diameter d H =32 nm; Sienna+(®), d H =59 nm; and ferumoxide, d H =111 nm), and a handheld magnetometer. Magnetometer counts (transcutaneous and ex vivo), iron quantification (vibrating sample magnetometry), and histopathological assessments were performed on all ex vivo nodes. RESULTS: Transcutaneous "hotspots" were present in 12/12 cases within 30 minutes of injection for the 59 nm tracer, compared to 7/12 for the 32 nm tracer and 8/12 for the 111 nm tracer, at the same time point. Ex vivo magnetometer counts were significantly greater for the 59 nm tracer than for the other tracers. Significantly more nodes per basin were excised for the 32 nm tracer compared to other tracers, indicating poor retention of the 32 nm tracer. Using the 59 nm tracer resulted in a significantly higher iron accumulation compared to the 32 nm tracer. CONCLUSION: The 59 nm tracer demonstrated rapid lymphatic uptake, retention in the first nodes reached, and accumulation in high concentration, making it the most suitable tracer for intraoperative sentinel lymph node localization.

T1-weighted MR image contrast around a cryoablation iceball: a phantom study and initial comparison with in vivo findings.

PURPOSE: To correlate T1-weighted (T1w) magnetic resonance (MR) image contrast around a cryoablation iceball with temperature in a phantom study and to compare this to its in vivo appearance during MR-guided focal cryoablation of prostate cancer. METHODS: A MR-compatible cryoneedle was inserted into identical gel phantoms (n = 3) on a 1.5 T MR system. Two fiber-optic temperature sensors were placed parallel to the needle. A fast 3D T1w gradient echo (GRE) sequence (TR/TE/FA = 4.81/1.98/6°) was used to monitor iceball progression. Normalized signal intensity (SI) was correlated with temperature. The same T1w sequence was used during MR-guided prostate cryoablation in ten consecutive patients at the authors' institution. In vivo findings were quantitatively compared to the phantom data. RESULTS: In the phantom study, the cryoablation iceball appeared in the T1w MR images as a sharply delineated signal void. A 2.2 ± 0.2 mm wide hyperintense rim directly surrounded the iceball at cooled but nonfreezing temperatures (<20 °C) in the gel. Normalized SI was maximum at 8.4 ± 2.4 °C, showing a 35.6%-43.0% (mean 40.5%) increase with respect to baseline before cooling. In the clinical procedures, the same image contrast was observed in vivo in all patients. In vivo, width of the hyperintense rim was 1.6 ± 0.6 mm. Normalized SI increases with respect to nontreated prostate ranged 28.4%-55.6% (mean 36.8%). On quantitative analysis, normalized SI changes along a linear region of interest from surrounding tissue onto the iceball center were similar between the patients and phantom setting (root mean square difference 0.06). CONCLUSIONS: The hyperintense rim around the iceball in fast T1w GRE images corresponded to cooled but nonfreezing temperatures (<20 °C) proximal to the frozen zone. The same image contrast was observed both in a phantom study as well as in vivo in the human prostate during cryotherapy. Potentially, monitoring of this rim could be useful in order to maintain a safe margin from at-risk tissues during MR-guided prostate cryoablation procedures.

Soft magnets from the self-organization of magnetic nanoparticles in twisted liquid crystals.

Organizing magnetic nanoparticles into long-range and dynamic assemblies would not only provide new insights into physical phenomena but also open opportunities for a wide spectrum of applications. In particular, a major challenge consists of the development of nanoparticle-based materials for which the remnant magnetization and coercive field can be controlled at room temperature. Our approach consists of promoting the self-organization of magnetic nanoparticles in liquid crystals (LCs). Using liquid crystals as organizing templates allows us to envision the design of tunable self-assemblies of magnetic nanoparticles, because liquid crystals are known to reorganize under a variety of external stimuli. Herein, we show that twisted liquid crystals can be used as efficient anisotropic templates for superparamagnetic nanoparticles and demonstrate the formation of hybrid soft magnets at room temperature.