Using Ultrasmall Superparamagnetic Iron Oxide Research Articles

Accuracy of Tumor Perfusion Assessment in Rat C6 Gliomas Model with USPIO.

Detailed characterization of the permeability and vascular volume of brain tumor vasculature can provide essential insights into tumor physiology. In this study, we evaluated the consistency of measurements in tumor blood volume and examined the feasibility of using ultrasmall superparamagnetic iron oxide (USPIO) versus gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) as contrast agents for MR perfusion imaging of brain gliomas in C6 Rats. Eighteen rats were intracerebrally implanted with C6 glioma cells, randomly divided into two groups and examined by 3.0T perfusion MR imaging with Gd-DTPA and USPIO. Tumor relative cerebral blood volume (rCBV) and relative maximum signal reduction ratio (rSRRmax) were created based on analysis of MR perfusion images. The mean values for rCBV were 2.09 and 1.57 in the USPIO and the Gd-DTPA groups, respectively, and rSRRmax values were 1.92 and 1.02 in the USPIO and the Gd-DTPA groups, respectively, showing signifi cant differences in both rCBV and rSRRmax between the USPIO and the Gd-DTPA groups (P < 0.05). The results showed that early vascular leakage occurred with gadolinium rather than USPIO in perfusion assessment, revealing that USPIO was useful in perfusion MR imaging for the assessment of tumor vasculature.

Detecting GPC3-Expressing Hepatocellular Carcinoma with L5 Peptide-Guided Pretargeting Approach: In Vitro and In Vivo MR Imaging Experiments.

Objective To investigate the potential of L5 peptide-guided pretargeting approach to identify GPC3-expressing hepatocellular carcinoma (HCC) using ultrasmall superparamagnetic iron oxide (USPIO) as the MR probe. Methods Immunofluorescence with carboxyfluorescein- (FAM-) labeled L5 peptide was performed in HepG2 cells. Polyethylene glycol-modified USPIO (PEG-USPIO) and its conjugation with streptavidin (SA-PEG-USPIO) were synthesized, and their hydrodynamic diameters, zeta potential, T2 relaxivity, and cytotoxicity were measured. In vitro and in vivo two-step pretargeting MR imaging was performed on HepG2 cells and tumor-bearing mice after the administration of biotinylated L5 peptide (first step), followed by SA-PEG-USPIO (second step). Prussian blue staining was performed to assess iron deposition in tumors. Results The high specificity of L5 peptide for GPC3 was demonstrated. Generation of SA-PEG-USPIO nanoparticles with good biocompatibility (an average hydrodynamic diameter of 35.97 nm and a zeta potential of −7.91 mV), superparamagnetism (R2 = 0.1039 × 103 mM−1s−1), and low toxicity was achieved. The pretargeting group showed more enhancement than the nonpretargeting group both in vitro (60% vs 20%, P < 0.05) and in vivo (32% vs 6%, P < 0.001). Substantial iron deposition was only observed in HepG2 cells and tumors in the pretargeting group. Conclusion L5 peptide-guided, two-step pretargeting approach with USPIO as the MR imaging probe is a lucrative strategy to specifically identify GPC3-expressing HCC.

Detecting GPC3-Expressing Hepatocellular Carcinoma with L5 Peptide-Guided Pretargeting Approach: An In Vitro MRI Experiment

Background and Aim : Glypican-3 (GPC3) is a novel molecular target for hepatocellular carcinoma (HCC). This study investigated the potential of an L5 peptide-guided pretargeting approach to identify GPC3-expressing HCC cells using ultra-small super-paramagnetic iron oxide (USPIO) as the MRI probe. Methods : Immunofluorescence with carboxyfluorescein (FAM)-labeled L5 peptide was performed in HepG 2 and HL-7702 cells. Polyethylene glycol-modified ultrasmall superparamagnetic iron oxide (PEG-USPIO) and its conjugates with streptavidin (SA-PEG-USPIO) were synthesized, and hydrodynamic diameters, zeta potential, T 2 relaxivity, and cytotoxicity were measured. MR T 2 -weighted imaging of HepG 2 was performed to observe signal changes in the pretargeting group, which was first incubated with biotinylated L5 peptide and then with SA-PEG-USPIO. Prussian blue staining of cells was used to assess iron deposition. Results : Immunofluorescence assays showed high specificity of L5 peptide for GPC3. SA-PEG-USPIO nanoparticles had ≈36 nm hydrodynamic diameter, low toxicity, negative charge and high T2 relaxivity. MR imaging revealed that a significant negative enhancement was only observed in HepG 2 cells from the pretargeting group, which also showed significant iron deposition with Prussian blue staining. Conclusion : MR imaging with USPIO as the probe has potential to identify GPC3-expressing HCC through L5 peptide-guided pretargeting approach.

Early monitoring and quantitative evaluation of macrophage infiltration after experimental traumatic brain injury: A magnetic resonance imaging and flow cytometric analysis.

The inflammatory response following traumatic brain injury (TBI) is regulated by phagocytic cells. These cells comprising resident microglia and infiltrating macrophages play a pivotal role in the interface between early detrimental and delayed beneficial effects of inflammation. The aim of the present study was to monitor the early effect of monocyte/phagocytic accumulation and further to explore its kinetics in TBI mice. Localized macrophage population was monitored using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle enhanced in vivo serial magnetic resonance imaging (MRI). Flow cytometry based gating study was performed to discriminate between resident microglia (Ly6G-CD11b+CD45low) and infiltrating macrophages (Ly6G-CD11b+CD45high) at the injury site. The T2* relaxation analysis revealed that maximum macrophage infiltration occurs between 66 and 72h post injury (42-48h post administration of USPIO) at the site of inflammation. This imaging data was well supported by iron oxide specific Prussian blue staining and macrophage specific F4/80 immunohistochemistry (IHC) analysis. Quantitative real-time PCR analysis found significant expression of monocyte chemoattractant protein-1 (MCP-1) at 72h post injury. Also, we found that flow cytometric analysis demonstrated a 7-fold increase in infiltrating macrophages around 72h post injuries as compared to control. The MR imaging in combination with flow cytometric analysis enabled the dynamic measurement of macrophage infiltration at the injury site. This study may help in setting an optimal time window to intervene and prevent damage due to inflammation and to increase the therapeutic efficacy.

Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in clinically isolated syndrome

Background: Macrophages are important components of inflammatory processes in multiple sclerosis, closely linked to axonal loss, and can now be observed in vivo using ultra-small superparamagnetic iron oxide (USPIO). In the present 1-year longitudinal study, we aimed to determine the prevalence and the impact on tissue injury of macrophage infiltration in patients after the first clinical event of multiple sclerosis. Methods: Thirty-five patients, 32 years mean age, were imaged in a mean of 66 days after their first event using conventional magnetic resonance imaging, gadolinium (Gd) to probe blood–brain barrier integrity, USPIO to study macrophage infiltration and magnetization transfer ratio (MTR) to assess tissue structure integrity. Statistics were performed using two-group repeated-measures ANOVA. Any patient received treatment at baseline. Results: At baseline, patients showed 17 USPIO-positive lesions reflecting infiltration of macrophages present from the onset. This infiltration was associated with local higher loss of tissue structure as emphasized by significant lower MTRnorm values (p<0.03) in USPIO+/Gd+ lesions (n=16; MTRnormUSPIO+/Gd+=0.78 at baseline, MTRnormUSPIO+/Gd+=0.81 at M12) relative to USPIO-/Gd+ lesions (n=67; MTRnormUSPIO-/Gd+=0.82 at baseline, MTRnormUSPIO–/Gd+=0.85 at M12). No interaction in MTR values was observed during the 12 months follow-up (lesion type × time). Conclusion: Infiltration of activated macrophages evidenced by USPIO enhancement, is present at the onset of multiple sclerosis and is associated with higher and persistent local loss of tissue structure. Macrophage infiltration affects more tissue structure while tissue recovery during the following year has a similar pattern for USPIO and Gd-enhanced lesions, leading to relative higher persistent local loss of tissue structure in lesions showing USPIO enhancement at baseline.

Mapping Radiation Injury and Recovery in Bone Marrow Using 18F-FLT PET/CT and USPIO MRI in a Rat Model.

We present and test the use of multimodality imaging as a topological tool to map the amount of the body exposed to ionizing radiation and the location of exposure, which are important indicators of survival and recovery. To achieve our goal, PET/CT imaging with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was used to measure cellular proliferation in bone marrow (BM), whereas MRI using ultra-small superparamagnetic iron oxide (USPIO) particles provided noninvasive information on radiation-induced vascular damage. Animals were x-ray-irradiated at a dose of 7.5 Gy with 1 of 3 radiation schemes-whole-body irradiation, half-body shielding (HBS), or 1-leg shielding (1LS)-and imaged repeatedly. The spatial information from the CT scan was used to segment the region corresponding to BM from the PET scan using algorithms developed in-house, allowing for quantification of proliferating cells, and BM blood volume was estimated by measuring the changes in the T2 relaxation rates (ΔR2) collected from MR scans. (18)F-FLT PET/CT imaging differentiated irradiated from unirradiated BM regions. Two days after irradiation, proliferation of 1LS animals was significantly lower than sham (P = 0.0001, femurs; P < 0.0001, tibias) and returned to sham levels by day 10 (P = 0.6344, femurs; P = 0.3962, tibias). The degree of shielding affected proliferation recovery, showing an increase in the irradiated BM of the femurs, but not the tibias, of HBS animals when compared with 1LS (P = 0.0310, femurs; P = 0.5832, tibias). MRI of irradiated spines detected radiation-induced BM vascular damage, measured by the significant increase in ΔR2 2 d after whole-body irradiation (P = 0.0022) and HBS (P = 0.0003) with a decreasing trend of values, returning to levels close to baseline over 10 d. Our data were corroborated using γ-counting and histopathology. We demonstrated that (18)F-FLT PET/CT and USPIO MRI are valuable tools in mapping regional radiation exposure and the effects of radiation on BM. Analysis of the (18)F-FLT signal allowed for a clear demarcation of exposed BM regions and elucidated the kinetics of BM recovery, whereas USPIO MRI was used to assess vascular damage and recovery.

Sequential Imaging of Asymptomatic Carotid Atheroma Using Ultrasmall Superparamagnetic Iron Oxide–enhanced Magnetic Resonance Imaging: A Feasibility Study

Inflammation within atheromatous plaques is a known risk factor for plaque vulnerability. This can be detected invivo on high-resolution magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide (USPIO) contrast medium. The purpose of this study was to assess the feasibility of performing sequential USPIO studies over a 1-year period. Ten patients with moderate asymptomatic carotid stenosis underwent carotid MRI imaging both before and 36 hours after USPIO infusion at 0, 6, and 12 months. Images were manually segmented into quadrants, and the signal change per quadrant was calculated at these time points. A mixed repeated measures statistical model was used to determine signal change attributable to USPIO uptake over time. All patients remained asymptomatic during the study. The mixed model revealed no statistical difference in USPIO uptake between the 3 time points. Intraclass correlation coefficients revealed a good agreement of quadrant signal pre-USPIO infusion between 0 and 6 months (0.70) and 0 and 12 months (0.70). Good agreement of quadrant signal after USPIO infusion was shown between 0 and 6 months (0.68) and moderate agreement was shown between 0 and 12 months (0.33). USPIO-enhanced sequential MRI of atheromatous carotid plaques is clinically feasible. This may have important implications for future longitudinal studies involving pharmacologic intervention in large patient cohorts.

Adipose Tissue Macrophages: MR Tracking to Monitor Obesity-associated Inflammation

To investigate whether cellular imaging by using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging can allow detection and quantification of adipose tissue macrophage-related inflammation within adipose tissue in a mouse model. Experimental protocols were conducted in accordance with French government policies. Adipose tissue macrophages were detected and quantified with a 4.7-T MR imager in ob/ob obese mice on the basis of the signal variance of adipose tissue triggered by injection of P904 iron oxide nanoparticles (USPIO). Mice were either intravenously injected with 1000 μmol of iron per kilogram of body weight of P904 (10 ob/ob and 11 ob/+) or used as noninjected control animals (seven ob/ob and six ob/+). Three-dimensional T2*-weighted gradient-echo MR images were acquired 10 days after intravenous injection. MR imaging signal variance in mice was correlated to adipose tissue macrophage quantification by using monoclonal antibody to F4/80 immunostaining, to proinflammatory marker quantification by using reverse transcription polymerase chain reaction (CCl2, Tnfα, Emr1), and to P904 quantification by using electron paramagnetic resonance imaging. Quantitative data were compared by using the Mann-Whitney or Student t test, and correlations were performed by using the Pearson correlation test. MR imaging measurements showed a significant increase in adipose tissue signal variance in ob/ob mice compared with ob/+ controls or noninjected animals (P < .0001), which was consistent with increased P904 uptake by adipose tissue in ob/ob mice. There was a significant and positive correlation between adipose tissue macrophage quantification at MR imaging and P904 iron oxide content (r = 0.87, P < .0001), adipose tissue macrophage-related inflammation at immunohistochemistry (r = 0.60, P < .01), and adipose tissue proinflammatory marker expression (r = 0.55, 0.56, and 0.58 for CCl2, Tnfα, and Emr1, respectively; P < .01). P904 USPIO-enhanced MR imaging is potentially a tool for noninvasive assessment of adipose tissue inflammation during experimental obesity. These results provide the basis for translation of MR imaging into clinical practice as a marker of patients at risk for metabolic syndrome.

USPIO-enhanced MRI of highly invasive and highly metastasizing transplanted human squamous cell carcinoma: an experimental study

The aim of this study was to investigate the signal intensity characteristics of highly invasive and highly metastasizing transplanted human squamous cell carcinoma using ultra-small super-paramagnetic iron oxide (USPIO)-enhanced MRI and to correlate them with USPIO distribution to tumour components revealed by histological examination. 13 nude mice with transplanted human squamous cell carcinoma in the oral cavity were imaged before and 24 hours after intravenous administration of USPIO. The difference in signal intensity between pre-contrast and post-contrast MR images was visually evaluated. For quantitative analysis, signal intensity within a region of interest was measured. Histological findings were correlated with MR findings. The approximate USPIO concentration was evaluated using USPIO phantoms. Seven tumours had an area showing signal intensity increase on post-contrast T₁ weighted images. Histopathologically, six of those tumours contained a small amount of iron particles in the stroma. The USPIO concentration was presumed low. Two tumours had an area showing signal intensity decrease on post-contrast T₁ and T₂ weighted images. The areas had a large amount of iron particles in the stroma and the USPIO concentration was presumed high. There was a minimal amount of iron particles in tumour parenchymal cells. The amount of USPIO accumulation into tumour stroma was considered to affect MR signal intensity. A small amount increases T₁ weighted signal intensity, whereas a large amount decreases T₁ and T₂ weighted intensity. The USPIO accumulation into the tumour parenchyma was not thought to affect MR signal intensity.

Evaluation of axillary lymph nodes by diffusion‐weighted MRI using ultrasmall superparamagnetic iron oxide in patients with breast cancer: Initial clinical experience

To investigate the diagnostic performance and clinical feasibility of diffusion-weighted magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes (ALNs) in patients with breast cancer. Sixteen patients with known breast cancer underwent 1.5 T MRI. Axial diffusion-weighted images (DWIs) and conventional T1- and T2*-weighted images (CIs) were acquired before and 24-36 hours after intravenous administration of USPIO. Detection of ALNs was evaluated on DWIs in comparison with CIs. The apparent diffusion coefficient values (ADCvs) of the nonmetastatic and metastatic nodes in precontrast DWIs were determined. The diagnostic performance of DWI using USPIO was compared with that of CIs using USPIO with pathological correlation. Out of a total of 286 ALNs, 216/286 (76%) nodes were detected on DWIs and 238/286 (83%) on CIs. The differences in the ADCvs between metastatic and nonmetastatic nodes were not significant (P = 0.06). Sensitivity of CIs and DWIs using USPIO were respectively 70% and 83%, specificity 98% and 98%, and overall accuracy 93% and 95%. Although the detection on DWIs of ALNs in patients with breast cancer was inferior compared to CIs, the sensitivity and accuracy of DWIs using USPIO were superior in the diagnosis of ALNs metastasis.

MRI of Macrophages in Infectious Knee Synovitis

The objective of our study was to prospectively evaluate macrophage imaging using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI to depict bacterial knee infection in an experimental rabbit model. Unilateral knee infection was induced by intraarticular injection of Staphylococcus aureus in eight rabbits. The contralateral knees were used as internal controls. After a mean interval of 3 days, two MRI sessions (3-T MRI) were performed before and 24 hours after IV administration of USPIO. The protocol included T1-weighted spin-echo, T2-weighted spin-echo, and T2*-weighted gradient-echo images. A gadolinium-enhanced T1-weighted sequence was also performed in the first session to optimize detection of synovial hyperplasia. MR data were analyzed qualitatively and quantitatively and compared with histopathologic findings (H and E stain and Perls Prussian blue stain). Signal-to-noise ratio changes after USPIO administration were compared using Wilcoxon's signed rank test. All inoculated knees presented infectious synovitis with intense infiltration of iron-loaded macrophages. In these infected knees, signal loss was determined visually and quantitatively on T1-weighted (p < 0.01), T2-weighted (p < 0.01), and T2*-weighted images (p < 0.01) 24 hours after USPIO administration, reflecting the presence of USPIO-loaded macrophages in the synovium. In contrast, no significant MR signal changes were observed in the control knees (p = 0.07-0.48), which presented a normal synovium without infiltration of iron-loaded macrophages. Macrophage imaging using USPIO-enhanced MRI can depict infectious knee synovitis.

The ATHEROMA Study: Rapid Anti-inflammatory Effects of High-Dose Statin Pharmacotherapy Illuminated by Molecular MRI

Statins are thought to reduce inflammation in atherosclerotic plaques; however, to date, in vivo data in clinical subjects demonstrating this effect and statin-dose dependency are limited. Molecular MRI of carotid plaque macrophage activity is well-validated using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and offers a novel clinical approach to assess the effects of antiinflammatory therapies in human subjects. Aims

High-resolution MR lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer: preliminary results

The purpose of this study was to examine the utility of high-resolution magnetic resonance (MR) lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer. Ten women with breast cancer without swollen axillary lymph nodes were enrolled in this study. High-resolution MR lymphography was performed 24h after administration of USPIO. On the MR examination, a 3-inch surface coil was placed on the sentinel lymph node (SLN) parts as defined by a radioisotope (RI) scintigraphy method, and T2*-weighted (T2*W) and T1-weighted (T1W) images were obtained. Detected nodes were differentiated as normal or diseased nodes by the enhancement patterns. The day after MR examination, SLN biopsy (SNB) was performed. The imaging results were compared to the histopathologic findings. On MR images, the mean number of detectable nodes was 7.9 per patient. Eight patients who histopathologically had no metastatic lymph nodes were diagnosed as nonmetastatic and two patients who had 3- and 6-mm metastatic areas in the node, respectively, were diagnosed as metastatic preoperatively. No side effects were noted. High-resolution MR lymphography using USPIO enabled us to obtain good axillary lymph node evaluation results. These results suggest that this method of imaging may contribute to better preoperative lymph node staging.

Locally Advanced Rectal Cancer: MR Imaging for Restaging after Neoadjuvant Radiation Therapy with Concomitant Chemotherapy Part II. What Are the Criteria to Predict Involved Lymph Nodes?

To prospectively determine diagnostic performance of predictive criteria for nodal restaging after radiation therapy with concomitant chemotherapy by using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging in patients with rectal cancer. After institutional review board approval and informed consent were obtained, 39 patients (24 men, 15 women; mean age, 64 years) with rectal cancer underwent USPIO-enhanced two-dimensional (2D) T2-weighted fast spin-echo, three-dimensional (3D) T1-weighted gradient-echo, and 3D T2*-weighted MR for restaging. Two observers evaluated nodes for border irregularity, short- and long-axis diameters, and estimated percentage of white region (<30%, 30%-50%, or >50%) within the node (3D T2*-weighted images). Ratio of the measured surface area of the white region within the black node to the measured surface area of the total node (Ratio(A)) was calculated. Signal intensity (SI) in gluteus muscle (SI(GM)) and in total node (SI(TN)) were used to calculate SI(TN)/SI(GM) ratio. Histopathologic findings were reference standard. Receiver operating characteristic (ROC) curves were compared and interobserver agreement was determined. Lesion-by-lesion analysis was feasible in 201 lymph nodes. Area under the ROC curve (AUC) of border and short- and long-axis diameters for observer 1 were 0.85, 0.87, and 0.88 and for observer 2 were 0.70, 0.89, and 0.87, respectively. AUC for estimated percentage of white region within the node, Ratio(A), and SI(TN)/SI(GM) ratio for observer 1 were 0.98, 0.99, and 0.62 and for observer 2 were 0.97, 0.98, and 0.65, respectively. AUC for USPIO-enhanced MR criteria was significantly better than AUC for conventional MR criteria (P < .01). All criteria except border irregularity and SI(TN)/SI(GM) ratio showed high interobserver agreement (kappa > 0.79). The most reliable predictors for identifying benign nodes after radiation therapy with concomitant chemotherapy by using USPIO-enhanced MR imaging for restaging in patients with rectal cancer were estimated percentage of white region within the node and Ratio(A). Measurements on standard 2D T2-weighted fast spin-echo images versus primary staging results offer reasonably good accuracy to identify benign lymph nodes after therapy.

Enhancement Characteristics of Ultrasmall Superparamagnetic Iron Oxide Particle Within the Prostate Gland in Patients With Primary Prostate Cancer

To analyze the enhancement of the prostate using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging in patients with prostate cancer. Sixty patients were enrolled. The signal-to-noise ratios (SNRs) of the central and peripheral zones (CZ and PZ, respectively) of the prostate were evaluated on T2- and T2*-weighted magnetic resonance imaging before and 24 hours after USPIO-enhanced MRI. The changes in SNR after USPIO-enhanced MRI were analyzed and correlated with serum prostate-specific antigen and histopathologic Gleason scoring based on surgically removed prostate gland. Decrease in SNR was noted in each zone of the prostate after USPIO-enhanced MRI (P < 0.001). Mean SNR decrease in the CZ was higher than that in the PZ (P < 0.05). High-grade prostate cancer was associated with a higher decrease in SNR (P < 0.05). The SNR change was negatively correlated with serum prostate-specific antigen at low or intermediate levels (P < 0.05). Enhancement of the prostate gland after USPIO administration may be associated with primary prostate cancer.

Correlation of Carotid Atheromatous Plaque Inflammation Using USPIO-Enhanced MR Imaging With Degree of Luminal Stenosis

Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The study explores the relationship between the degree of Magnetic Resonance (MR)-defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles and the severity of luminal stenosis in asymptomatic carotid plaques. Seventy-one patients with an asymptomatic carotid stenosis of > or = 40% underwent multi-sequence USPIO-enhanced MR imaging. Stenosis severity was measured according to the NASCET and ECST methods. No demonstrable relationship between inflammation as measured by USPIO-enhanced signal change and the degree of luminal stenosis was found. Inflammation and stenosis are likely to be independent risk factors, although this needs to be further validated.

Comparison of the Inflammatory Burden of Truly Asymptomatic Carotid Atheroma with Atherosclerotic Plaques in Patients with Asymptomatic Carotid Stenosis Undergoing Coronary Artery Bypass Grafting: An Ultrasmall Superparamagnetic Iron Oxide Enhanced Magnetic Resonance Study

Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p<0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p<0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p=0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p<0.001). These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques contralateral to symptomatic carotid stenosis: an ultra small superparamagnetic iron oxide enhanced magnetic resonance study

Background:Inflammation is a recognised risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of magnetic resonance...

Evaluation of lymph node metastases of breast cancer using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging

Background We assessed the utility of enhanced magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph node metastases in patients with breast cancer. Study design MR examination of the axilla was performed before and 24–36 h after USPIO administration for patients with stage II or III breast cancer. Diagnostic performance was compared using size criteria (metastasis was defined when short axis diameter >5 or >10 mm) or morphologic criteria on conventional MRI, the combined study of USPIO precontrast and postcontrast images, and USPIO postcontrast study alone. Results A total of 622 nodes (503 metastatic and 119 nonmetastatic nodes) were dissected from 33 patients. The results of conventional MRI for nodes >5 mm were 59.1% sensitivity, 86.7% specificity, and 80.4% overall accuracy. Results for nodes >10 mm were 15.7% sensitivity, 99.2% specificity, and 80.2% overall accuracy. Results based on morphology were 36.5% sensitivity, 94.1% specificity, and 81.0% overall accuracy. The results of the combined study of USPIO precontrast and postcontrast images were 86.4% sensitivity, 97.5% specificity, 91.1% positive predictive value, 96.1% negative predictive value, and 95.0% overall accuracy. The results of USPIO postcontrast images alone were 84.7% sensitivity, 96.8% specificity, and 94.0% overall accuracy. Patient-based results of postcontrast USPIO study alone were 100.0% sensitivity, 80.0% specificity, and 93.9% overall accuracy. Conclusions USPIO postcontrast study alone was useful in the assessment of axillary lymph node metastases in patients with breast cancer.

Correlation of carotid atheromatous plaque inflammation with biomechanical stress: Utility of USPIO enhanced MR imaging and finite element analysis

Objective The aim of this study was to explore whether there is a relationship between the degree of MR-defined inflammation using ultra small super-paramagnetic iron oxide (USPIO) particles, and biomechanical stress using finite element analysis (FEA) techniques, in carotid atheromatous plaques. Methods and Results 18 patients with angiographically proven carotid stenoses underwent multi-sequence MR imaging before and 36 h after USPIO infusion. T 2 * weighted images were manually segmented into quadrants and the signal change in each quadrant normalised to adjacent muscle was calculated after USPIO administration. Plaque geometry was obtained from the rest of the multi-sequence dataset and used within a FEA model to predict maximal stress concentration within each slice. Subsequently, a new statistical model was developed to explicitly investigate the form of the relationship between biomechanical stress and signal change. The Spearman's rank correlation coefficient for USPIO enhanced signal change and maximal biomechanical stress was −0.60 ( p = 0.009). Conclusions There is an association between biomechanical stress and USPIO enhanced MR-defined inflammation within carotid atheroma, both known risk factors for plaque vulnerability. This underlines the complex interaction between physiological processes and biomechanical mechanisms in the development of carotid atheroma. However, this is preliminary data that will need validation in a larger cohort of patients.