SPIO-enhanced Magnetic Resonance Imaging Research Articles

Targeted trapping of endogenous endothelial progenitor cells for myocardial ischemic injury repair through neutrophil-mediated SPIO nanoparticle-conjugated CD34 antibody delivery and imaging

Endothelia progenitor cell (EPC)-based revascularization therapies have shown promise for the treatment of myocardial ischemic injury. However, applications and efficacy are limited by the relatively inefficient recruitment of endogenous EPCs to the ischemic area, while implantation of exogenous EPCs carries the risk of tumorigenicity. In this study, we developed a therapeutic protocol that relies on the capacity of neutrophils (NEs) to target lesions and release preloaded EPC-binding molecules for high efficiency capture. Neutrophils were loaded with superparamagnetic iron oxide nanoparticles conjugated to an antibody against the EPC surface marker CD34 (SPIO-antiCD34/NEs), and the therapeutic efficacy in ischemic mouse heart following SPIO-antiCD34/NEs injection was monitored by SPIO-enhanced magnetic resonance imaging (MRI). These SPIO-antiCD34/NEs exhibited unimpaired cell viability, superoxide generation, and chemotaxis in vitro as well as satisfactory biocompatibility in vivo. In a mouse model of acute myocardial infarction (MI), SPIO-antiCD34 accumulation could be observed 0.5 h after intravenous injection of SPIO-antiCD34/NEs. Moreover, the degree of CD133+ EPC accumulation at MI sites was three-fold higher than in control MI model mice, while ensuing microvessel density was roughly two-fold higher than controls and left ventricular ejection fraction was > 50%. Therapeutic cell biodistribution, MI site targeting, and treatment effects were confirmed by SPIO-enhanced MRI. This study offers a new strategy to improve the endogenous EPC-based myocardial ischemic injury repair through NEs mediated SPIO nanoparticle conjugated CD34 antibody delivery and imaging. Statement of SignificanceThe efficacy of endogenous endothelial progenitor cell (EPC)-based cardiovascular repair therapy for ischemic heart damage is limited by relatively low EPC accumulation at the target site. We have developed a method to improve EPC capture by exploiting the strong targeting ability of neutrophils (NEs) to ischemic inflammatory foci and the capacity of these treated cells to release of preloaded cargo with EPC-binding affinity. Briefly, NEs were loaded with superparamagnetic iron oxide nanoparticles conjugated to an antibody against the EPC surface protein CD34 (SPIO-antiCD34). Thus, we explored sites targeting with nanocomposites cargo for non-invasive EPCs interception and therapy tracking. We demonstrate that SPIO-antiCD34 released from NEs can effectively capture endogenous EPCs and thereby promote heart revascularization and functional recovery in mice. Moreover, the entire process can be monitored by SPIO-enhanced magnetic resonance imaging including therapeutic cell biodistribution, myocardial infarction site targeting, and tissue repair.

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.

Superparamagnetic iron oxide-enhanced magnetic resonance imaging is useful in predicting malignant potential of vascular transformation of hypointense hypovascular nodules on gadoxetic acid-enhanced magnetic resonance imaging.

To examine whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) can be used to assess the malignant potential of hepatic hypovascular nodules showing hypointensity during the hepatobiliary phase (HBP) on gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI. The study included 42 patients with chronic liver disease who had small hypovascular nodules (5-15mm) showing hypointensity during the HBP on Gd-EOB-DTPA-enhanced MRI. The SPIO-enhanced T2-weighted MRI analyzed whether the signal intensity of each nodule was high. Nodules were prospectively followed up until hypervascularization by periodic Gd-EOB-DTPA-enhanced MRI. Initial MRI findings and clinical variables were used to analyze predictive factors for hypervascularization. We analyzed 77 nodules, of which 19 (25%) showed hypervascularization during the observation period. The cumulative rates for hypervascularization were 11% and 22% at 1 and 2years, respectively. Hyperintensity was observed in 12 nodules (16%) on SPIO-enhanced T2-weighted MRI; among these, 7 (58%) showed hypervascularization, whereas 12 (18%) of the remaining 65 nodules without hyperintensity showed hypervascularization (P = 0.007). A Cox model revealed that independent predictors of hypervascularization included hyperintense nodules on SPIO-enhanced MRI (P <0.001). The cumulative rates for hypervascularization in hyperintense nodules on SPIO-enhanced MRI were 52% at 1year, whereas these rates were 3% for non-hyperintense nodules. Superparamagnetic iron oxide-enhanced MRI is useful for predicting the malignant potential of vascular transformation of hypovascular nodules with hypointensity observed in the HBP on Gd-EOB-DTPA-enhanced MRI.

Superparamagnetic iron oxide-enhanced magnetic resonance imaging for focal hepatic lesions: systematic review and meta-analysis.

To evaluate the performance of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the detection and characterization of focal hepatic lesions (FHLs). This meta-analysis compared relevant studies that were identified by searching PubMed, EMBASE, and the Cochrane Library databases for articles published between January 1988 and September 2014 and that met the following criteria: (1) SPIO-enhanced MRI was conducted to identify FHLs and data were sufficient for pooled analysis using Meta-DiSc 1.4; (2) hepatocellular carcinomas (HCCs) were differentiated from other FHLs; (3) well-differentiated HCCs (WD-HCCs) were contradistinguished from dysplastic nodules; and (4) WD-HCCs were compared with moderately and poorly differentiated HCCs (MD- and PD-HCCs, respectively). The data obtained from 15 eligible studies yielded a sensitivity of 85% and a specificity of 78% for differentiating between HCCs and other FHLs. The sensitivity was unchanged and the specificity was increased to 87% when non-HCC malignancies were excluded. Comparative analyses between WD-HCCs and MD- and PD-HCCs from seven studies showed a sensitivity of 98% and a specificity of 50% for the diagnosis of MD- and PD-HCCs, and the area under the summary receiver operating characteristics (sROC) curve was 0.97. A comparison between WD-HCCs and dysplastic nodules revealed a sensitivity of 50% and a specificity of 92% for the diagnosis of WD-HCCs and the area under the sROC curve was 0.80. SPIO-enhanced MRI is useful in differentiating between HCCs and other FHLs.

SPIO-enhanced MR imaging at 3T for accurate diagnosis of sentinel node metastases to avoid sentinel node biopsy in patients with breast cancer.

68 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging at 1.5T for the detection of metastases in sentinel nodes identified by computed tomography lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol 2011, ASCO 2012). The aim of this study was to evaluate whether SPIO-enhanced MR imaging at 3T improved the diagnostic accuracy for the detection of metastases in sentinel nodes. Moreover, these results were compared with those of the diagnosis using CT-LG according to the size criteria. Methods: Seventy patients with breast cancer and clinically negative nodes were included. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging at 3T. Sentinel node size was measured on CT-LG and a node larger than 5 mm in short axis diameter was considered metastatic. Sentinel nodes localized by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 55 years (range, 29-78). Sentinel nodes were identified by CT-LG successfully in 69 (98.6%) of 70 patients. The mean number of sentinel nodes identified by CT-LG was 1.4 (range, 1-3). All 19 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Forty-eight of 50 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on the imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 100%, 96.0%, and 97.1%, respectively, on a patient-by-patient basis. Those of CT-LG were 78.9%, 56.0%, 62.3%, respectively. The specificity and accuracy of MR imaging were superior to those of CT-LG (McNemar test; p &lt; .0001 and = .0015, respectively). Conclusions: SPIO-enhanced MR imaging at 3T can accurately diagnose the sentinel node metastases, and therefore sentinel node biopsy may not be required for most patients with breast cancer.

Quantitative evaluation of the reticuloendothelial system function with dynamic MRI.

PurposeTo evaluate the reticuloendothelial system (RES) function by real-time imaging blood clearance as well as hepatic uptake of superparamagnetic iron oxide nanoparticle (SPIO) using dynamic magnetic resonance imaging (MRI) with two-compartment pharmacokinetic modeling.Materials and MethodsKinetics of blood clearance and hepatic accumulation were recorded in young adult male 01b74 athymic nude mice by dynamic T2* weighted MRI after the injection of different doses of SPIO nanoparticles (0.5, 3 or 10 mg Fe/kg). Association parameter, Kin, dissociation parameter, Kout, and elimination constant, Ke, derived from dynamic data with two-compartment model, were used to describe active binding to Kupffer cells and extrahepatic clearance. The clodrosome and liposome were utilized to deplete macrophages and block the RES function to evaluate the capability of the kinetic parameters for investigation of macrophage function and density.ResultsThe two-compartment model provided a good description for all data and showed a low sum squared residual for all mice (0.27±0.03). A lower Kin, a lower Kout and a lower Ke were found after clodrosome treatment, whereas a lower Kin, a higher Kout and a lower Ke were observed after liposome treatment in comparison to saline treatment (P<0.005).ConclusionDynamic SPIO-enhanced MR imaging with two-compartment modeling can provide information on RES function on both a cell number and receptor function level.

Is imaging the future of axillary staging in breast cancer?

Axillary management in patients with breast cancer has become much less invasive with the introduction of sentinel lymph node biopsy (SLNB). However, over 70% of SLNBs are negative, questioning the generic use of this invasive procedure. Emerging evidence indicates that breast cancer patients with a low axillary burden of disease do not benefit from axillary lymph node dissection (ALND). Non-invasive techniques such as paramagnetic iron oxide contrast-enhanced magnetic resonance imaging (MRI) may provide genuine alternatives to axillary staging and should be evaluated within clinical trials. Selective axillary surgery could then be offered based on imaging findings and for therapeutic intent. This non-operative approach would reduce morbidity further and facilitate interpretation of follow-up imaging. Key Points • Modern imaging and biopsy greatly help the axillary staging of breast cancer. • Superparamagnetic iron oxide (SPIO)-enhanced MRI offers a further advance. • Sentinel lymph node biopsy may become redundant with SPIO-enhanced MRI. • Selective therapeutic axillary surgery should be based upon preoperative imaging findings.

Correlation between the area of high-signal intensity on SPIO-enhanced MR imaging and the pathologic size of sentinel node metastases in breast cancer patients with positive sentinel nodes

BackgroundWe previously demonstrated that superparamagnetic iron oxide (SPIO)-enhanced MR imaging is promising for the detection of metastases in sentinel nodes localized by CT-lymphography in patients with breast cancer. The purpose of this study was to determine the predictive criteria of the size of nodal metastases with SPIO-enhanced MR imaging in breast cancer, with histopathologic findings as reference standard.MethodsThis study included 150 patients with breast cancer. The patterns of SPIO uptake for positive sentinel nodes were classified into three; uniform high-signal intensity, partial high-signal intensity involving ≥50% of the node, and partial high-signal intensity involving <50% of the node. Imaging results were correlated with histopathologic findings.ResultsThirty-three pathologically positive sentinel nodes from 30 patients were evaluated. High-signal intensity patterns that were uniform or involved ≥50% of the node were observed in 23 nodes that contained macro-metastases and no node that contained micro-metastases, while high-signal intensity patterns involving <50% of the node were observed in 2 nodes that contained macro-metastases and 8 nodes that contained micro-metastases. When the area of high-signal intensity was compared with the pathological size of the metastases, a pathologic >2 mm sentinel node metastases correlated with the area of high-signal intensity, however, a pathologic ≤2 mm sentinel node metastases did not.ConclusionsHigh-signal intensity patterns that are uniform or involve ≥50% of the node are features of nodes with macro-metastases. The area of high-signal intensity correlated with the pathological size of metastases for nodes with metastases >2 mm in this series.

SPIO-enhanced MR imaging at 3T for the detection of metastases in sentinel nodes in patients with breast cancer.

1107 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging at 1.5T for the detection of metastases in sentinel nodes localized by computed tomography lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol 2011, ASCO 2012). The aim of this study was to evaluate the accuracy of MR imaging at 3T with SPIO enhancement for the detection of metastases in sentinel nodes. Methods: This study included 60 patients with breast cancer and clinically negative nodes. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging at 3T. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show a low signal intensity on MR imaging. Sentinel nodes located by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 54.2 years (range, 33-78). Sentinel nodes were identified by CT-LG successfully in 59 (98.3%) of 60 patients. The mean number of sentinel nodes identified by CT-LG was 1.43 (range, 1-3). All 16 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Five (31.3%) of them had micrometastases. Forty-one of 43 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 100%, 95.3%, and 96.6%, respectively. No adverse events were associated with either CT or MR imaging. Conclusions: SPIO-enhanced MR imaging at 3T is useful for accurate diagnosis of sentinel node metastases, and therefore sentinel node biopsy may be avoided for most patients with breast cancer.

Preliminary experience with superparamagnetic iron oxide-enhanced dynamic magnetic resonance imaging and comparison with contrast-enhanced computed tomography in endoleak detection after endovascular aneurysm repair

Contrast-enhanced computed tomography (CE-CT) has been commonly used for follow-up imaging after endovascular aneurysm repair (EVAR), but it is difficult to use on patients with renal insufficiency. Superparamagnetic iron oxide (SPIO) particles, contrast medium for magnetic resonance imaging (MRI) that has been widely used for detection of the liver tumor, rarely affects renal function. The present study examined SPIO-enhanced dynamic MRI as a potential alternative to CE-CT for detection of endoleaks after EVAR. Institutional review board approval was obtained for this prospective study. Twenty-three consecutive patients with normal renal function were evaluated using both CE-CT and SPIO-enhanced MRI within 2 weeks after EVAR. The median interval between the two modalities was 2 days. SPIO-enhanced MRI was performed at 1.5 T with T1-weighted, SPIO-enhanced dynamic, and postcontrast T1-weighted gradient echo sequences. The CE-CT protocol consisted of triple scans. Two experienced, blinded observers evaluated all images. Consensus reading of CE-CT and SPIO-MRI was defined as the reference standard. Interobserver, intraobserver, and intermodality agreement for endoleak detection was assessed by κ statistics. A total of 11 type II endoleaks originating from either the lumbar or inferior mesenteric artery were detected. Eight were able to be detected by CE-CT (8/11:73%) and 10 (10/11:91%) by SPIO-enhanced MRI. Interobserver (κ = 0.91; 95% CI, 0.74-1.00) and intraobserver agreement for MRI (κ = 1.00) were excellent. Intermodality agreement for endoleak detection was moderate (κ = 0.63; 95% CI, 0.32-0.94; and κ = 0.62; 95% CI, 0.29-0.95 for observers A and B, respectively). SPIO-enhanced MRI could represent a useful alternative to CE-CT, as it offers excellent interobserver, intraobserver agreement, and could detect more endoleaks than CE-CT.

Deposition of superparamagnetic iron‐oxide nanoparticles in axillary sentinel lymph nodes following subcutaneous injection

Superparamagnetic iron oxide nanoparticle (SPIO)-enhanced axillary lymph node magnetic resonance imaging (MRI) has the potential to supersede sentinel lymph node (SLN) biopsy in the management of early breast cancer with in vivo pre-operative metastasis detection. We evaluated the distribution and extent of SPIOs within the SLN and its impact on routine histological assessment. A total of 131 SLNs from 51 consecutive patients with breast cancer were examined histologically following subcutaneous injection of 2-4ml SPIOs. SLNs were identified intra-operatively using the combined technique. Ex vivo histological analysis was performed and the distribution of SPIOs assessed using standard haematoxylin and eosin staining. SPIO distribution was predominantly within lymph node sinuses (81%); fewer nodes contained iron in the subcapsular space (24%) and parenchyma (14%). In 58%, SPIOs were sequestered in macrophages. SPIOs were not seen within the areas of nodes containing metastases, but was seen surrounding the metastases. Following subcutaneous injection of SPIOs, iron deposition is found predominantly in sinuses and the subcapsular space and is not found in areas containing metastases. This reinforces the notion that high resolution SPIO-enhanced MRI has the potential for in vivo metastasis in the SLN in breast cancer. Routine histological examination was unaffected.

Sentinel node biopsy for breast cancer: past, present, and future

Sentinel node biopsy has replaced axillary lymph node dissection as the standard of care in early breast cancers. Sentinel node biopsy represents a highly accurate and less-morbid axillary staging, which allows most patients to avoid unnecessary axillary lymph node dissection and its morbidity. This review provides information including several issues which are still under debate, such as clinical significance of micrometastases, avoidance of axillary lymph node dissection for patients with positive sentinel nodes, accuracy and timing of sentinel node biopsy in patients undergoing neoadjuvant chemotherapy, and how many sentinel nodes are sufficient for removal. Finally, a new topic is introduced: superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging for the detection of metastases in sentinel nodes localized by computed tomography (CT)-lymphography (CT-LG) in patients with breast cancer. SPIO-enhanced MR imaging is a useful method of detecting metastases in sentinel nodes localized by CT-LG in patients with breast cancer. Patients with clinically negative nodes may be spared even sentinel node biopsy when the sentinel node is diagnosed as disease free using SPIO-enhanced MR imaging.

Evaluation of the uptake function of liver in rats with obstructive jaundice before and after relief from obstruction by superparamagnetic iron oxide-enhanced magnetic resonance imaging

The aim of this study was to investigate the changes in the uptake function of the liver in rats with obstructive jaundice prior to and following relief from obstructive jaundice, and to investigate whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) could be used to assess liver uptake function. In total, 40 male Sprague Dawley rats were randomly assigned into four groups: Obstructive jaundice, internal drainage, external drainage and sham surgery. The common bile ducts in the obstructive jaundice group were ligated. Internal drainage (ID) and external drainage (ED) groups were ligated, followed by internal drainage or external drainage, respectively. The T2 and T2* values of the liver parenchyma were measured. Liver sections were stained with Perls' Prussian blue, and hematoxylin and eosin. The number of SPIO-nanoparticle clusters was counted manually using a microscope. Total bilirubin of the blood was measured. Results showed that the T2 and T2* values and total bilirubin of the obstructive jaundice group were significantly higher compared to the other three groups. The number of SPIO-nanoparticle clusters in the obstructive jaundice group was significantly lower compared to the other three groups. In conclusion, obstructive jaundice suppresses liver uptake function in rats, which may be reversed by internal and external biliary drainage. However, no significant difference was found between the therapeutic effect of ID and ED on liver uptake function. Thus, SPIO-enhanced MRI may be used to evaluate the uptake function of the liver.

SPIO-enhanced MR imaging for axillary staging to avoid sentinel node biopsy in patients with breast cancer.

1103 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging for the detection of metastases in sentinel nodes localized by computed tomography (CT) lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol, 2011). These techniques have evolved and we report our most recent results of axillary staging using them. Methods: Previously unreported 87 consecutive patients with breast cancer and clinically negative nodes were enrolled in this study. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show a low signal intensity on MR imaging. Sentinel nodes located by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 54.9 years (range, 34-77). Sentinel nodes were identified by CT-LG and removed successfully in all patients. The mean number of sentinel nodes identified by CT-LG was 1.16 (range, 1-2). Twenty of 22 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Fifty-eight of 65 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 91%, 89%, and 90%, respectively. Two patients whose metastases were not detected had micrometastases. No adverse events were associated with either CT or MR imaging. Conclusions: SPIO-enhanced MR imaging provided accurate axillary staging, and therefore sentinel node biopsy may not be necessary for most patients with breast cancer.

Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI

Determination of lymphatic metastasis is of great importance for both treatment planning and patient prognosis. We aim to distinguish tumor metastatic lymph nodes (TLNs) and reactive lymph nodes (RLNs) with diffusion-weighted and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI). Ipsilateral popliteal lymph node metastasis or lymphadenitis model was established by hock injection of either luciferase-expressing 4T1 murine breast cancer cells or complete Freund's adjuvant in male BALB/c mice. At different time points after inoculation, bioluminescence imaging and T(2)-weighted, diffusion-weighted, and SPIO-enhanced MRI were performed. Imaging findings were confirmed by histopathological staining. Size enlargement was observed in both TLNs and RLNs. At day 28, TLNs showed strong bioluminescence signal and bigger size than RLNs (p < 0.01). At early stages up to day 21, both TLNs and RLNs appeared homogeneous on diffusion-weighted imaging. At day 28, TLNs showed heterogeneous apparent diffusion coefficient (ADC) map with significantly higher average ADC value of 0.41 ± 0.03 × 10(-3)mm(2)/s than that of RLNs (0.34 ± 0.02 × 10(-3)mm(2)/s; p < 0.05). On SPIO-enhanced MRI, both TLNs and RLNs showed distinct T(2) signal reduction at day 21 after inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide particles, which was confirmed by Prussian blue staining. Both diffusion-weighted and SPIO-enhanced MRI can distinguish tumor metastatic lymph nodes from reactive lymph nodes. However, neither method is able to detect tumor metastasis to the draining lymph nodes at early stages.

529 Correlation Between the Area of High-signal Intensity on SPIO-enhanced MR Imaging and the Pathologic Size of Sentinel Node Metastases in Breast Cancer Patients with Positive Sentinel Nodes

529 Correlation Between the Area of High-signal Intensity on SPIO-enhanced MR Imaging and the Pathologic Size of Sentinel Node Metastases in Breast Cancer Patients with Positive Sentinel Nodes

MR Characterization of Focal Nodular Hyperplasia: Gadoxetic Acid versus Superparamagnetic Iron Oxide Imaging

We evaluated the diagnostic efficacy of gadoxetic acid- and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging for focal nodular hyperplasia (FNH). We retrospectively evaluated 11 patients with 11 FNHs. Both gadoxetic acid- and SPIO-enhanced MR imaging were performed. A 3-dimensional (3D) volumetric interpolated breath-hold examination was used with the gadoxetic acid dynamic study. SPIO-enhanced MR imaging included T₂- and T₂*-weighted images. We quantitatively and qualitatively compared lesion-specific enhancement of both contrast media. The mean signal-to-noise (S/N) ratio of the FNH lesions differed significantly on pre- and postenhanced imaging of each contrast medium (P<0.05); mean contrast-to-noise (C/N) ratio did not (P>0.05). All observers described all lesions as hyperintense in the arterial phase on gadoxetic acid-enhanced MR imaging and observed the presence of central scar, fibrous septa, and rim most clearly in gadoxetic acid-enhanced hepatobiliary phase images. Gadoxetic acid-enhanced MR imaging was more useful than SPIO-enhanced MR imaging in characterizing FNH.

P3-07-46: Accuracy of SPIO-Enhanced MR Imaging Alone for the Diagnosis of Sentinel Node Metastases in Patients with Breast Cancer.

Abstract Background Superparamagnetic iron oxide (SPIO)-enhanced MR imaging has been reported to be promising for the detection of metastases in sentinel nodes localized by CT lymphography in patients with breast cancer (Motomura, Ann Surg Oncol 2011). The current SPIO technique involves imaging before and after contrast administration. This study evaluated the accuracy of SPIO-enhanced MR imaging alone without unenhanced imaging. Methods: This study included 120 patients with breast cancer demonstrating clinically negative nodes. Sentinel nodes were identified by CT lymphography, and MR imaging of the axilla before and 18–24 hr after interstitial administration of SPIO was performed. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if there was an absence of low signal intensity either in the entire node or in a focal area on SPIO-enhanced MR imaging. The diagnostic accuracy of the SPIO-enhanced imaging alone was compared with that of combined unenhanced and SPIO-enhanced imaging. Results: The mean number of sentinel nodes identified by CT lymphography was 1.2 (range 1–3). Pathologic evaluation demonstrated that 28 (23.3%) of 120 patients showed metastasis to at least one node. One false negative result was added when the evaluation was based solely on SPIO-enhanced MR imaging. Consequently, the sensitivity decreased from 84.0% to 80.0% and the accuracy decreased from 89.2% to 88.3%, respectively, in the SPIO-enhanced MR imaging alone. However, the differences in sensitivity and accuracy between SPIO-enhanced MR imaging alone and the combined unenhanced and SPIO-enhanced imaging were not significant (McNemar's test; p=1.0). The specificity of enhanced imaging alone and that of combined unenhanced and SPIO-enhanced imaging were both 90.5%. Conclusions: A single MR imaging examination performed after SPIO administration can be used for accurate diagnosis of sentinel node metastases, and thus reduce the time and cost of imaging. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-46.

In Vivo Imaging of Stepwise Vessel Occlusion in Cerebral Photothrombosis of Mice by 19F MRI

Background 19F magnetic resonance imaging (MRI) was recently introduced as a promising technique for in vivo cell tracking. In the present study we compared 19F MRI with iron-enhanced MRI in mice with photothrombosis (PT) at 7 Tesla. PT represents a model of focal cerebral ischemia exhibiting acute vessel occlusion and delayed neuroinflammation.Methods/Principal FindingsPerfluorocarbons (PFC) or superparamagnetic iron oxide particles (SPIO) were injected intravenously at different time points after photothrombotic infarction. While administration of PFC directly after PT induction led to a strong 19F signal throughout the entire lesion, two hours delayed application resulted in a rim-like 19F signal at the outer edge of the lesion. These findings closely resembled the distribution of signal loss on T2-weighted MRI seen after SPIO injection reflecting intravascular accumulation of iron particles trapped in vessel thrombi as confirmed histologically. By sequential administration of two chemically shifted PFC compounds 0 and 2 hours after illumination the different spatial distribution of the 19F markers (infarct core/rim) could be visualized in the same animal. When PFC were applied at day 6 the fluorine marker was only detected after long acquisition times ex vivo. SPIO-enhanced MRI showed slight signal loss in vivo which was much more prominent ex vivo indicative for neuroinflammation at this late lesion stage.ConclusionOur study shows that vessel occlusion can be followed in vivo by 19F and SPIO-enhanced high-field MRI while in vivo imaging of neuroinflammation remains challenging. The timing of contrast agent application was the major determinant of the underlying processes depicted by both imaging techniques. Importantly, sequential application of different PFC compounds allowed depiction of ongoing vessel occlusion from the core to the margin of the ischemic lesions in a single MRI measurement.

Estimating the Need for Neck Lymphadenectomy in Submucosal Esophageal Cancer Using Superparamagnetic Iron Oxide‐Enhanced Magnetic Resonance Imaging: Clinical Validation Study

In cases of thoracic esophageal cancer, multidirectional lymphatic flow from the tumor means that lymph node metastasis can occur in an area extending from the neck to the abdomen. To validate a method for limiting the performance of three-field lymphadenectomy only to patients who need it, we carried out a prospective study in which superparamagnetic iron oxide (SPIO)-enhanced lymphatic mapping was used to determine whether to perform neck lymph node dissection in patients with submucosal thoracic esophageal cancer. A total of 22 patients with clinically submucosal thoracic squamous cell esophageal cancer, without neck lymph node metastasis, were enrolled. SPIO was endoscopically injected into the peritumoral submucosal layer, after which its appearance in lymph nodes in the neck was evaluated using magnetic resonance imaging (MRI). Neck lymph nodes were then dissected based on the SPIO-enhanced MRI lymphatic mapping. Influx of SPIO into lymph nodes was detected in 21 patients (95% detection rate). SPIO flowed to the neck in 8 (36%) patients. Influx of SPIO into neck lymph nodes was unilateral in five patients and bilateral in three patients, and the lymph nodes were dissected accordingly. A cancer-involved node was identified in two of those patients. In 14 patients, we did not dissect neck nodes. Patients were followed up for 6 to 47 months. The neck lymph node recurrence rate was zero, and the overall recurrence rate was 5%. SPIO-enhanced lymphatic mapping may be useful for estimating the need for three-field lymphadenectomy with neck dissection.