Injection Of Superparamagnetic Iron Oxide Research Articles

Avoiding unnecessary sentinel lymph node biopsy with the use of superparamagnetic iron oxide mapping agents (Magtrace®) in breast surgery.

Superparamagnetic iron oxide (SPIO) (Magtrace®) is a non-radioactive liquid tracer that can stay in the sentinel lymph nodes for 30 days. Injection of SPIO at time of primary breast surgery where upfront sentinel lymph node biopsy (SLNB) is not immediately indicated allows for a return to theatre if pathology then identifies invasive disease. SLNB is associated with paraesthesia, pain, seroma formation and lymphoedema risk. Hence, our study aims to assess the use of SPIO to avoid upfront SLNB in breast surgery for ductal carcinoma in situ (DCIS) and prophylaxis. Retrospective single-centre study of consecutive patients who underwent injection of SPIO tracer at time of primary breast surgery to avoid upfront SLNB at Chris O'Brien Lifehouse, Sydney, NSW, Australia over a 10-month period. SPIO was injected 38 times, with 34 at time of mastectomy and four cases at time of wide local excision. The indication for surgery was DCIS in 18 cases, risk reduction in 17 cases and other indications in three patients. Six cases (15.8%) required delayed SLNB (D-SLNB) due to the finding of invasive disease on post-operative histopathology. All patients who underwent D-SLNB had nodes successfully localized with SPIO. In our cohort, 84.2% of cases were able to avoid upfront SLNB, and hence avoid the associated complications of SLNB. SPIO injection was successful in localizing the SLN in all cases at time of surgery for D-SLNB. This technique was safe with few associated complications.

Sentinel lymph node biopsy in a resourcelimited setting: a retrospective comparison of sentinel lymph node biopsy before and after the introduction of Sentimag at an academic breast unit.

Sentinel lymph node biopsy (SLNB) is performed for staging and prognostication of breast cancer (BC) in cases with a clinically and radiologically negative axilla. Using blue dye and a radioactive colloid injection is considered the gold standard for SLNB. This study aims to evaluate the SLNB outcomes before and after the introduction of Sentimag at an academic breast unit. Sentimag uses an injection of superparamagnetic iron oxide which is then detected in the sentinal lymph node using a magnetometer. A retrospective cohort study was performed comparing SLNBs done from 1 January 2017 to 31 December 2018. During 2017, a nuclear medicine technique was used for all SLNBs, while the Sentimag system was used in 2018. There was no difference between the two groups comparing age, T-stage, size of tumour, and molecular status. The only statistically significant difference found was more higher-grade tumours in the group where a nuclear medicine technique was used in 2017 (p = 0.04). There was no difference in the type of surgery performed comparing mastectomy and breast-conserving surgery rates between the two groups. There was an 11% increase in the number of patients who had an SLNB done with the Sentimag technique (2018). In 2017, 42% (58/139) had an SLNB and in 2018, 53% (59/112) had an SLNB. This result demonstrates the feasibility of the magnetic technique for SLNB in a resource-limited setting. This new method shows promise as a safe and effective technique for SLNB - it is a valuable alternative in the absence of nuclear medicine (N.Med) facilities.

ASO Author Reflections: Pre-Operative Injection of Superparamagnetic Iron Oxide as the Only Localizing Tracer in Sentinel Lymph Node Biopsy in Early Breast Cancer.

ASO Author Reflections: Pre-Operative Injection of Superparamagnetic Iron Oxide as the Only Localizing Tracer in Sentinel Lymph Node Biopsy in Early Breast Cancer.

Patients’ perception of skin discolouration caused by the injection of superparamagnetic iron oxide (SPIO) for sentinel node biopsy in breast cancer: Just a slight inconvenience or a serious problem?

Patients’ perception of skin discolouration caused by the injection of superparamagnetic iron oxide (SPIO) for sentinel node biopsy in breast cancer: Just a slight inconvenience or a serious problem?

Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study

BackgroundDifficulty in preoperatively assessing the risk for occult invasion or surgery that precludes future accurate axillary mapping in patients with ductal cancer in situ (DCIS) account for overutilization of SLND.MethodsProspective, multicenter, cohort study, including women with any DCIS planned for mastectomy or DCIS grade 2 and > 20 mm, any DCIS grade 3, any mass-forming DCIS and any planned surgery. Patients received an interstitial SPIO injection during breast surgery, but no upfront SLND was performed. If invasion was identified on final pathology, delayed SLND (d-SLND) was performed separately with the coadministration of isotope ± blue dye (BD). Study outcomes were proportion of upfront SLNDs that were avoided, detection rates during d-SLND, and impact on healthcare costs.ResultsIn total, 78.7% of study participants (N = 254, mean age 60 years, mean DCIS size 37.8 mm) avoided upfront SLND. On d-SLND (median 28 days, range 9–46), SPIO outperformed Tc99 with (98.2% vs. 63.6%, p < 0.001) or without BD (92.7% vs. 50.9%, p < 0.001) and had higher nodal detection rate (86.9% vs. 32.3%, p < 0.001) and with BD (93.9% vs. 41.4%, p < 0.001). Only 27.9% of all SLNs retrieved were concordant for Tc99 and SPIO. Type of breast procedure (WLE vs. oncoplastic BCT vs. mastectomy) affected these outcomes and accounted for the low performance of Tc99 (p < 0.001). d-SLND resulted in a 28.1% total cost containment for women with pure DCIS on final pathology (4190 vs. 5828 USD, p < 0.001).ConclusionsMarking the SLN with SPIO may avoid overtreatment and allow for accurate d-SLND in patients with DCIS.

Superparamagnetic Iron Oxide Nanoparticles Directed miRNA-34b-RNA-Binding Proteins T Cell to Restrict Intracellular Antigen-1-Stress Granules (TIA-1-SG) in Breast Cancer Chemotherapy

miRNA-34b-T cell restricted intracellular antigen-1-stress granules (miRNA-34b-TIA-1-SG) superparamagnetic iron oxide nanoparticles were studied in this project and their directional function will provide a new carrier for improving directional improvement of interventional therapeutic drugs for breast cancer. We explored its therapeutic effect on breast cancer treatment through the following groups; Group I: blank control group (injected with 0.9% normal saline 0.5 mL to the tail vein), Group II: miRNA-34b-TIA-1-SG group (superparamagnetic iron oxide miRNA-34b-TIA-1-SG nanoparticles given by tail vein injection), Group III: superparamagnetic iron oxide-oriented miRNA-34b-TIA-1-SG group (superparamagnetic iron oxide nanoparticles given by tail vein injection). In vitro experiment involved the following methods: MTT, flow cytometry and colony formation experiment, all used to evaluate biological processes of tumor cells after tail vein injection of superparamagnetic iron oxide directed miRNA-34b-TIA-1-SG. In vivo experiments involved the following: tumor xenotransplantation experiment, used to observe the effect of tail vein injection of superparamagnetic iron oxide-oriented miRNA-34b-TIA-1-SG on the treatment effect of breast cancer. Both In vivo experiments and In vitro experiments in MDA-MB-231 cells confirmed that superparamagnetic iron oxide-oriented miRNA-34b-TIA-1-SG nanoparticles effectively inhibited breast cancer cells proliferation and colony formation, and also promoted cell apoptosis. Promotion of cell apoptosis is one of the main ways to treat breast cancer, as appearance of stress granules inhibits cell apoptosis, so regulating stress granules to promote the apoptosis of breast cancer cells is an important treatment strategy. TIA-1 is an essential component of stress granules, and miRNA-34b was significantly down-regulated in breast cancer cells. Therefore, the hypothesis that miRNA-34b-TIA-1-SG signal axis regulates cell apoptosis and promotes breast cancer cell proliferation is herein proposed. We constructed the miRNA-34b reporter gene system, and our study showed that the superparamagnetic iron oxide oriented miRNA-34b-TIA-1-SG nanoparticles may be used as a development direction for breast cancer treatment, which may provide a new and highly effective molecular-oriented drug.

MR lymphography with superparamagnetic iron oxide for sentinel lymph node mapping of N0 early oral cancer: A pilot study.

The purpose of this pilot study was to evaluate the usefulness of magnetic resonance lymphography (MRL) with superparamagnetic iron oxide (SPIO) in sentinel lymph node (SLN) mapping of clinically N0 early oral cancer, and to conduct a comparative study of this MRL with CT lymphography (CTL). CTL and MRL were performed for SLN mapping before surgery for 20 patients with clinically N0 early oral cancer. The detection rate, number, and location of SLNs in CTL and MRL were evaluated. Furthermore, optimal scanning/imaging timing in MRL was examined. SLNs were detected by CTL in 18 (90%) patients, and the total and mean number of SLN were 35 and 1.8, respectively. All SLNs could be detected 2 min and 3.5-5 min after contrast medium injection. In all patients, SLNs were detected by MRL at 10 min after SPIO injection, and the total and mean number of SLN was 53 and 2.7, respectively. MRL at 30 min after the injection showed additional 18 secondary lymph nodes. MRL with SPIO is safe and useful imaging for the detection of SLNs in clinically N0 early oral cancer, and the optimal imaging timing is 10 min after SPIO injection.

Detection of Macrophage Localization in the Abdominal Aortic Aneurysm Wall Using Ex Vivo Superparamagnetic Iron Oxide–Enhanced Magnetic Resonance Imaging

Macrophages in the aneurysmal wall play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Superparamagnetic iron oxide (SPIO) is a macrophage-specific contrast agent that results in negative enhancement on magnetic resonance imaging (MRI). SPIO-enhanced MRI targeting the intraluminal thrombus of AAAs has been previously reported. However, macrophages in the media and adventitia of AAA wall have not been investigated in detail. This study aimed to evaluate macrophage localization using SPIO-enhanced MRI in the media and adventitia of AAA wall, as macrophages play a crucial role in AAA pathogenesis. Here, we included study and control patients planning to undergo open surgery for AAA. The study patients received SPIO injection 2days preoperatively (the SPIO group, n=7), whereas the control patients did not receive this injection (the control group). Exvivo MRI was performed on the harvested AAA wall in the SPIO group during the surgery. The concordance between the number of macrophages and berlin blue (BB)-stained areas was histologically evaluated in both groups. Moreover, the concordance between regions of interest in MR images and BB-stained areas was evaluated. The proportion of BB-stained macrophages was higher in the SPIO group (0.93; interquartile range [IQR], 0.83-0.95) than in the control group (0.03; IQR, 0.026-0.11) (P<0.05), indicating uptake of SPIO by macrophages in the AAA wall. A significant positive correlation was found between the number of BB-stained macrophages and BB-stained areas using Kendall rank correlation coefficient in the SPIO group (τ=0.58; P<0.05). Significant correlations were found in the distributions of the region of interest of SPIO-enhanced MRI and BB-stained areas in the media and adventitia in 5 of 7 patients. Macrophages present in the media and adventitia of the AAA wall showed an uptake of the SPIO contrast agent injected 2days prior, which were then detected by exvivo MRI. This suggests that SPIO-enhanced MR images help detect the localization of macrophages on the AAA wall, indicating its potential to serve as a novel index for AAA pathogenesis.

Magnetic brain stimulation using iron oxide nanoparticle-mediated selective treatment of the left prelimbic cortex as a novel strategy to rapidly improve depressive-like symptoms in mice

Magnetic brain stimulation has greatly contributed to the advancement of neuroscience. However, challenges remain in the power of penetration and precision of magnetic stimulation, especially in small animals. Here, a novel combined magnetic stimulation system (c-MSS) was established for brain stimulation in mice. The c-MSS uses a mild magnetic pulse sequence and injection of superparamagnetic iron oxide (SPIO) nanodrugs to elevate local cortical susceptibility. After imaging of the SPIO nanoparticles in the left prelimbic (PrL) cortex in mice, we determined their safety and physical characteristics. Depressive-like behavior was established in mice using a chronic unpredictable mild stress (CUMS) model. SPIO nanodrugs were then delivered precisely to the left PrL cortex using in situ injection. A 0.1 T magnetic field (adjustable frequency) was used for magnetic stimulation (5 min/session, two sessions daily). Biomarkers representing therapeutic effects were measured before and after c-MSS intervention. Results showed that c-MSS rapidly improved depressive-like symptoms in CUMS mice after stimulation with a 10 Hz field for 5 d, combined with increased brain-derived neurotrophic factor (BDNF) and inactivation of hypothalamic-pituitary-adrenal (HPA) axis function, which enhanced neuronal activity due to SPIO nanoparticle-mediated effects. The c-MSS was safe and effective, representing a novel approach in the selective stimulation of arbitrary cortical targets in small animals, playing a bioelectric role in neural circuit regulation, including antidepressant effects in CUMS mice. This expands the potential applications of magnetic stimulation and progresses brain research towards clinical application.

Skin staining following injection of superparamagnetic iron oxide (SPIO) for sentinel node biopsy in breast cancer: How often, how wide, how long?

Skin staining following injection of superparamagnetic iron oxide (SPIO) for sentinel node biopsy in breast cancer: How often, how wide, how long?

Abstract P3-01-11: Discoloration after injection of super paramagnetic iron oxide (SPIO) for sentinel node biopsy. A long term qualitative follow-up study

Abstract Background SPIO has a similar detection ratio as Technetium99 and Patent Blue to identify sentinel nodes (SN). No allergic reactions have been observed and no nuclear medicine facilities are needed, making logistics easier. At the Academic Hospital in Uppsala, Sweden, SPIO has been used routinely for three years. After breast conserving surgery (BCS) many women developed a brownish discoloration at the injection site. The discoloration stays for a long time. To study the patient-experienced cosmetic discomfort and the natural history of the discoloration we followed our first 153 BCS women for more than two years. After modifying the technique of injection we registered the discoloration in the following 115 women. Methods All women injected with a retro-areolar injection of SPIO between April 2015 and October 2016 were included. The women were telephone interviewed every third month. The size of the discoloration was self-assessed and the cosmetic discomfort was classified by a scale from 0 (no discomfort) to 5 points (very discomforting). Photos were taken in selected cases after 1-2 years. Between November 2016 and April 2017, a deeper, para-tumoral injection was used and discoloration was noted 3 weeks after surgery. Results Ninety of 153 women (58.8%) developed a discoloration after a retro-areolar injection. The mean size was 26.1cm2 (2-100cm2). The discoloration had vanished in 6.8% and 11.4% of the women after 1 and 2 years, respectively. The mean size of the discolorations was 18.2cm2 (1-66cm2) and 13.6cm2 (1-66cm2) after 1 and 2 years. The intensity of the color was continuously fading. The cosmetic discomfort was assessed as 2.2 points after 1 year and 1.0 after 2 years. Of 115 women with a deeper injection, 32.2% developed a discoloration with a mean size of 13.1cm2 (1-36cm2), three weeks after surgery. The incidence and size of the discolorations were statistically significantly less and smaller after a deeper injection (p&amp;lt;0.001 and p=0.001, respectively). SNs were identified in 91% of women with a retro-areolar injection and in 93% of those with a deeper injection. Conclusions After an injection of SPIO, a discoloration might develop and the discoloration can stay for more than 2 years in many women. However, the color fades and the size diminish continuously and the women do not consider the discoloration a major cosmetic problem. A deeper injection reduces the incidence and the size of the discoloration with a similar detection ratio of SN. In our next study, we aim to reduce the volume of SPIO and thereby hopefully reduce the discoloration. Patient-assessed cosmetic discomfort after 1 and 2 yearsPatient age1 year2 years&amp;lt;55 years3.10.9≥55 years1.91.00=no discomfort, 5=very discomforting Citation Format: Wärnberg M, Karakatsanis A, Abdsaleh S, Wärnberg F. Discoloration after injection of super paramagnetic iron oxide (SPIO) for sentinel node biopsy. A long term qualitative follow-up study [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 P3-01-11.

Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer.

Sentinel node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles is a novel method in breast cancer. Several studies have verified the non-inferiority of SPIO compared with the standard use of radioisotope 99m Tc with or without blue dye. The aim of the MONOS study presented here was to evaluate the use of SPIO as a sole tracer and the efficacy of tracer injection in the preoperative setting. This prospective cohort study was carried out in two hospitals, one using 99m Tc and the other SPIO. 99m Tc was injected in the morning of the day of surgery or the day before. SPIO was either injected before surgery in the outpatient clinic or 1 h before the operation. A total of 338 consecutive patients with breast cancer underwent 343 procedures; SPIO nanoparticles were used in 184 procedures and 99m Tc-labelled tracer in 159. Detection rates for SPIO and 99m Tc were 95·6 and 96·9 per cent respectively (P = 0·537). All nodes with SPIO uptake were coloured brown. Fewer nodes were retrieved with SPIO (mean 1·35 versus 1·89), regardless of whether blue dye was used (P < 0·001). Preoperative SPIO injection (58·7 per cent of procedures), a median of 16 (range 2-27) days before the procedure, was associated with a better tracer-specific detection rate (95·3 versus 86 per cent; P = 0·031) and retrieval of more nodes (mean 1·43 versus 1·03; P < 0·001) than perioperative administration. Skin staining was present in 39·9 per cent of patients, and was related to breast-conserving surgery and periareolar injection. The use of SPIO alone is a safe alternative, with results comparable to those of the standard dual technique using 99m Tc and blue dye. The efficacy of injection in the preoperative setting simplifies logistics and improves performance. Skin staining can be prevented by a deeper peritumoral injection.

Photoacoustic staging of nodal metastases using SPIOs: Comparison between in vivo, in toto and ex vivo imaging in a rat model

Background and objectives: To determine prognosis and treatment, accurate nodal staging is essential in many tumor types. After injection of clinical grade superparamagnetic iron oxide (SPIO) nanoparticles, it has been shown that metastatic lymph nodes can be distinguished from benign specimens using MR imaging. However, MR does not benefit per-operative nodal staging which requires a non-ionizing, small volume, high resolution, fast imaging technique. In vivo non-invasive photoacoustic (PA) imaging of lymph nodes might facilitate nodal staging during surgery, thereby benefiting both surgeon and patient. Materials and methods: In order to investigate the feasibility of an in vivo nodal staging approach using photoacoustics, six Mat-lylu inoculated Copenhagen rats were photo-acoustically imaged after injection of a new Class IIa medical device SPIO magnetic tracer (Sienna+). Lymph nodes were imaged in vivo, in toto (after euthanization) and ex vivo using multiple wavelength illumination. Results were compared with MRI, immunohistochemistry and photographs of the sectioned nodes. Results: These experiments demonstrate that in an ex vivo setting, the PA contrast of Sienna+ is able to facilitate a distinction between metastatic and benign nodes. A non-invasive distinction between both groups is partially impeded by the low amount of PA contrast generated by the SPIO particles compared to that of endogenous absorbers such as hemoglobins. Conclusions: This comparison between in vivo, in toto and ex vivo PA imaging of lymph nodes after SPIO injection demonstrates that the clinical potential of combined PA/SPIO staging should initially be exploited in an ex vivo setting. Improved distinction between chromophores by for example multi-spectral unmixing might in the near future enable non-invasive assessment of nodal involvement.

Targeted transplantation of iron oxide-labeled, adipose-derived mesenchymal stem cells in promoting meniscus regeneration following a rabbit massive meniscal defect.

Repair of a massive meniscal defect remains a challenge in the clinic. However, targeted magnetic cell delivery, an emerging technique, may be useful in its treatment. The present study aimed to determine the effect of targeted intra-articular injection of superparamagnetic iron oxide (SPIO)-labeled adipose-derived mesenchymal stem cells (ASCs) in a rabbit model of a massive meniscal defect. ASCs may be directly labeled and almost 100% of the ASCs were labeled with SPIO after 24 h; these SPIO-labeled ASCs may be orientated by magnet. The centrifuged SPIO-labeled ASCs precipitations may be detected by magnetic resonance imaging (MRI). The anterior half of the medial meniscus of 18 New Zealand Rabbits was excised. After 7 days, the rabbits were randomized to injections of 2×106 SPIO-labeled ASCs, 2×106 unlabeled ASCs or saline. Permanent magnets were fixed to the outside of the operated joints for one day, and after 6 and 12 weeks, the knee joints were examined using MRI, gross and histological observation, and Prussian blue staining. Marked hypointense artifacts caused by SPIO-positive cells in the meniscus were detected using MRI. Histological observation revealed that the anterior portion of the meniscus was similar to the native tissue, demonstrating typical fibrochondrocytes surrounded by richer extracellular matrix in the SPIO-ASCs group. Collagen-rich matrix bridging the interface and the neo-meniscus integrated well with its host meniscus. Furthermore, degenerative changes occurred in all groups, but intra-articular injection of SPIO-ASCs or ASCs alleviated these degenerative changes. Prussian blue staining indicated that the implanted ASCs were directly associated with the regenerated tissue. Overall, targeted intra-articular delivery of SPIO-ASCs promoted meniscal regeneration whilst providing protective effects from osteoarthritic damage.

Combined Preclinical Magnetic Particle Imaging andMagnetic Resonance Imaging: Initial Results inMice.

Magnetic particle imaging (MPI) is a new radiologic imaging modality. For the first time, a commercial preclinical scanner is installed. The goal of this study was to establish a workflow between MPI and magnetic resonance imaging (MRI) scanners for a complete in vivo examination of a mouse and to generate the first co-registered in vivo MR-MP images. The in vivo examination of five mice were performed on a preclinical MPI scanner and a 7 Tesla preclinical MRI system. MRI measurements were used for anatomical referencing and validation of the injection of superparamagnetic iron oxide (SPIO) particles during a dynamic MPI scan. We extracted MPI data of the injection phase and co-registered it with MRI data. A workflow process for a combined in vivo MRI and MPI examination was established. A successful injection of ferucarbotran was proven in MPI and MRI. MR-MPI co-registration allocated the SPIOs in the inferior vena cava and the heart during and shortly after the injection. The acquisition of preclinical MPI and MRI data is feasible and allows the combined analysis of MR-MPI information.

Adriamycin‐induced nephropathy in rats: Functional and cellular effects characterized by MRI

To assess with magnetic resonance imaging (MRI) adriamycin-induced nephropathy in living rats, an established model for proteinuric renal disease was used. Functional information of contrast agent clearance was obtained with dynamic contrast-enhanced (DCE) imaging following intravenous Gd-DOTA administration. Perfusion data were obtained with a bolus tracking technique comprising intravenous injection of superparamagnetic iron oxide (SPIO) nanoparticles. Cellular information was derived from anatomical images acquired 24 hours after SPIO. Treatment with the transforming growth factor-β123 (TGF-β1,2,3 ) antibody, 1D11, started 1 week after adriamycin. Histology was performed at week 6 post-adriamycin. Tracer washout rates derived by DCE-MRI decreased by 65.5% with respect to baseline at week 6 post-adriamycin. The impaired kidney function agreed with glomerulopathy, nephropathy and fibrosis revealed histologically (picrosirius collagen staining in adriamycin-treated rats increased by 125.8% [P = 0.005] with respect to controls). Perfusion was reduced by 16.1%. Images acquired 24 hours after SPIO presented contrast changes that correlated inversely with the histologically determined iron content (R = -0.74, P = 2.6 × 10(-4) ). In adriamycin-challenged animals, iron was found in macrophages and in sclerotic tubuli, only in areas where macrophages were present. Treatment with 1D11 did not improve the adriamycin-induced renal injury. MRI provides longitudinal functional and cellular (macrophage infiltration) information that correlates with nephropathy development in adriamycin-challenged rats.

Sentinel Lymph Node Detection in Patients with Oral Cancer by MR Lymphography using Superparamagnetic Iron Oxide

The purpose of this study was to examine the feasibility of interstitial MR lymphography using Superparamagnetic Iron Oxide (SPIO) to detect sentinel lymph nodes (SLNs) in head and neck cancer. For two patients with cT2N0 squamous cell carcinoma of the tongue, the submucosal injection of SPIO as well as sentinel lymph node navigation surgery (SLNNS) was performed before undergoing surgical treatment. SPIO was used for MR lymphography and Tc-99m phytate for SPECT. We compared the images by both modalities. Berlin blue stain was also performed postoperatively to verify if SLNs had the uptake of SPIO. The lymph nodes with MR signal attenuation and those with hot spots were probed to be anatomically identical. All the lymph nodes detected as a SLN by a gamma-probe contained the blue granules from SPIO. These data suggest that SPIO can be a novel tracer for performing SLNNS and SLN biopsy (SLNB) in oral cancer patients with cN0 neck.

In Vivo Imaging of Macrophages during the Early-Stages of Abdominal Aortic Aneurysm Using High Resolution MRI in ApoE−/− Mice

BackgroundAngiotensin II (ANG II) promotes vascular inflammation and induces abdominal aortic aneurysm (AAA) in hyperlipidemic apolipoprotein E knock-out (apoE−/−) mice. The aim of the present study was to detect macrophage activities in an ANG II-induced early-stage AAA model using superparamagnetic iron oxide (SPIO) as a marker.Methodology/Principal FindingsTwenty-six male apoE−/− mice received saline or ANG II (1000 or 500 ng/kg/min) infusion for 14 days. All animals underwent MRI scanning following administration of SPIO with the exception of three mice in the 1000 ng ANG II group, which were scanned without SPIO administration. MR imaging was performed using black-blood T2 to proton density -weighted multi-spin multi-echo sequence. In vivo MRI measurement of SPIO uptake and abdominal aortic diameter were obtained. Prussian blue, CD68,α-SMC and MAC3 immunohistological stains were used for the detection of SPIO, macrophages and smooth muscle cells. ANG II infusion with 1000 ng/kg/min induced AAA in all of the apoE−/− mice. ANG II infusion exhibited significantly higher degrees of SPIO uptake, which was detected using MRI as a distinct loss of signal intensity. The contrast-to-noise ratio value decreased in proportion to an increase in the number of iron-laden macrophages in the aneurysm. The aneurysmal vessel wall in both groups of ANG II treated mice contained more iron-positive macrophages than saline-treated mice. However, the presence of cells capable of phagocytosing haemosiderin in mural thrombi also induced low-signal-intensities via MRI imaging.Conclusions/SignificanceSPIO is taken up by macrophages in the shoulder and the outer layer of AAA. This alters the MRI signaling properties and can be used in imaging inflammation associated with AAA. It is important to compare images of the aorta before and after SPIO injection.

Diffusion-Weighted MR Imaging before and after Contrast Enhancement with Superparamagnetic Iron Oxide for Assessment of Hepatic Metastasis

PurposeThe purpose of our study was to validate diffusion-weighted MRI (DWI) before and after superparamagnetic iron oxide (SPIO) injection for assessment of hepatic metastases.Materials and MethodsEighty-six hepatic metastases (size range, 0.3-4.7 cm; mean, 1.5 cm) verified pathologically or by follow-up imaging studies in 22 consecutive patients (17 men and 5 women; 44-83 years; mean age, 60 years) during a 13-month period were enrolled. Hepatic MRI, including DWI (b-factors=50, 400, 800 s/mm2) with breath-holding technique of single-shot spin-echo echo-planar imaging (TR/TE=1000/69 ms, average=2) before and after SPIO administration, were retrospectively reviewed by two independent radiologists with a 5-point scale confidence score for each hepatic lesion on pre-contrast DWI (pre-DWI), SPIO-enhanced DWI (SPIO-DWI), and SPIO-enhanced T2*-weighted imaging (SPIO-T2*wI).ResultsFor all lesions, SPIO-T2*wI showed significantly higher confidence score in the diagnosis of hepatic metastases than pre-contrast or SPIO-DWI regardless of the size of b-factors (p<0.05) with only one exception; using b-factor=50 s/mm2, the score of SPIO-T2*wI was still higher than SPIO-DWI but there was no statistical significance given by observer 1 (p=0.730). For the subcentimeter lesions (n=37), SPIO-T2*wI showed the highest score, and using b-factor=50 or 400 s/mm2 SPIO-DWI showed similar confidence scores to SPIO-T2*wI by both observers (p>0.05). Pre-DWI using b-factor=50 sec/mm2 was also comparable with SPIO-T2*wI by observer 1 (p=0.060).ConclusionPre-DWI has a limited value for the assessment of hepatic metastases, however, the repetition of DWI after SPIO injection using small b-factors could complement SPIO-T2*wI, especially for subcentimeter lesions.

P2-08-07: Ex-Vivo High Resolution MRI of Sentinel Lymph Nodes Following Subcutaneous Injection of Superparamagnetic Iron Oxide Nanoparticles.

Abstract Background: Superparamagnetic iron oxide (SPIO) enhanced axillary MRI is a promising novel imaging modality that could be used to characterize sentinel nodes non-invasively. In order to better characterize lymph nodes and evaluate their morphological features, we imaged nodes ex-vivo using high resolution MRI, following a pre-operative subcutaneous injection of SPIO. Material and methods: Prior to surgery patients received a circumareolar injection of SPIO (Endorem, Guerbet, Paris) into the upper outer quadrant of the affected breast. Sentinel lymph nodes excised during surgery were transported to the imaging department fresh. Nodes were placed in glass tubes and scanned using a Bruker 9.4T MRI system (T2 mapping: turbo spin echo, 16 equi-spaced TEs from 7.1 to 113.6 ms, TR = 1616 ms. T2* mapping: gradient echo, 6 equi-spaced TEs from 3.5 to 21 ms, TR = 1000 ms, flip angle = 30 degrees. Diffusion-weighted: spin echo, b-values 0 and 1000 s/mm2, TE = 18 ms, TR = 6500 ms.). Slice thickness was 1 mm with an in plane spatial resolution of 100μm. Image analysis was undertaken using Osirix (v3.8, 64-bit). Results: A total of 40 nodes were successfully imaged, excised from 14 patients. The internal architecture of nodes was clearly seen and in the 3 involved nodes, a macrometastasis was identified. Three patients received a 4ml injection of SPIO and 11 patients, a 2ml injection. More SPIO deposition was seen within nodal sinuses following 4ml of SPIO, but there was no significant decrease in mean T2 value. Four nodes were re-imaged following formalin fixation and nodal architecture was unchanged with a trend towards an increase in mean T2 values within nodes. SPIO was identified in all sentinel nodes. Discussion: Ex-vivo MRI with subcutaneous SPIO contrast, is a useful method for imaging and characterization of sentinel nodes. A better understanding of ex-vivo features is a useful aide to understanding the morphological features seen following in-vivo SPIO enhanced axillary MRI. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-07.