Superparamagnetic Iron Oxide-enhanced Magnetic Resonance Imaging Research Articles

Monitoring of impaired phagocytic function of Kupffer cells in an obstructive cholangitis rat model using superparamagnetic iron oxide MRI and contrast-enhanced ultrasound.

Kupffer cells (KC) have an important role in the host defense in obstructive cholangitis. Non-invasive monitoring of phagocytic function of KC is pivotal. Several studies showed the possibility of non-invasive monitoring of phagocytic function of KC using superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) or contrast-enhanced ultrasound (CEUS). To investigate the serial change of KC function using SPIO-MRI and CEUS and whether the SPIO-MRI parameter correlates with the CEUS parameter in obstructive cholangitis rat models. With our institutional Animal Care and Use Committee approval, 19 rats (common bile duct ligation [CBDL]: n = 9; control: n = 10) underwent SPIO-MRI and CEUS at baseline, two, and four weeks after CBDL. The relative signal loss (RSL) of T2* value on SPIO-MRI and Kupffer phase parenchymal echogenicity (KPE) on CEUS were measured. The correlation between SPIO-MRI and CEUS parameters were compared with KC count. In CBDL group, RSL and KPE had significantly decreased (72.1% to 29.5%, 2.7 to 0.4) at four weeks compared with those in the control group (68.2% to 58.3%, 2.5 to 3.0, P < 0.05). During the follow-up period, RSL showed significantly positive correlations with KPE ( P = 0.007). In addition, at four weeks, we found RSL was positively correlated with KPE (ρ = 0.750, P = 0.002). KC count was negatively correlated to RSL and KPE at four weeks (ρ = -0.771, P = 0.001 and ρ = -0.644, P = 0.013). SPIO-MRI and CEUS may be equally useful for monitoring the serial changes of KC phagocytic function invivo.

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.

Phagocytic function of Kupffer cells in mouse nonalcoholic fatty liver disease models: Evaluation with superparamagnetic iron oxide.

To evaluate the Kupffer cell (KC) phagocytic function using superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) in animal models with nonalcoholic fatty liver disease (NAFLD). Mouse NAFLD models with varying severity were created by feeding high-fat, high-cholesterol (HFHC) diets to ob/ob mice for 3, 6, or 12 weeks. SPIO-MRI was performed on a 4.7-T animal scanner in the mouse NAFLD models, in wildtype control mouse, and in the NAFLD mice (NAFLD treatment group) that received 6 weeks of pioglitazone treatment. The relative signal loss (RSL) of the liver was measured in each animal to represent the magnitude of SPIO-induced signal loss of the liver. Liver samples were analyzed for steatosis, inflammation, fibrosis, and the number of SPIO particles and KCs. RSL values of the NAFLD mice (range of RSL value, 26.3%-53.8%) seen on SPIO-MRI were significantly lower than those of the control mice (67.7%-74.8%, P ≤ 0.008) and decreased in proportion to the duration of their HFHC diet (mean ± SD, 53.7% ± 10.9, 44.7% ± 8.2, and 26.3% ± 12.6, after 3-, 6-, and 12-week HFHC diet, respectively, on 20-minute delayed images). For the NAFLD treatment group, the RSL values increased after 6 weeks of pioglitazone treatment, compared with the values before treatment (P ≤ 0.039). The RSL values had significant independent correlation with both hepatic steatosis (P = 0.007) and inflammation (P = 0.023). KC phagocytic dysfunction is aggravated in the progression of NAFLD and may be reversible with therapeutic intervention. SPIO-MRI may be useful for classifying the severity of NAFLD and monitoring the treatment response of NAFLD.

Delayed hepatic signal recovery on ferucarbotran-enhanced magnetic resonance images in a rat model with regional liver irradiation

To determine whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging could demonstrate signal recovery delay in irradiated areas of rat livers. We also investigated the relationship between MR imaging and histological findings. Twelve rats received 20μmol iron/kg of SPIO followed by X-irradiation to the right upper abdomen 4h later. Radiation doses were 0, 50 and 70Gy. Hepatic signals were assessed on unenhanced T 2 (*) -weighted images for up to 7days using a 9.4-Tesla scanner. The livers were excised on day 7 and examined histologically. Normalized relative signal intensity of 70Gy-irradiated right liver lobe (2.36±0.22) and 50Gy-irradiated right liver lobe (2.37±0.46) was significantly lower than that of the non-irradiated right liver lobe (4.04±0.28) on day 7, respectively (p<0.05). Pearson product-moment correlation coefficient between relative intensity of the liver and the number of hepatic iron deposits was -0.588 (p<0.01). Superparamagnetic iron oxide-enhanced MR imaging could demonstrate signal recovery delay in irradiated areas of rat livers. It seems that the signal recovery delay in irradiated areas was due to SPIO-derived iron deposition. Hepatic signal recovery could be a novel diagnostic marker for delineation of irradiated areas.

Assessment of Disease Activity in Multiple Sclerosis Phenotypes with Combined Gadolinium- and Superparamagnetic Iron Oxide–enhanced MR Imaging

To compare magnetic resonance (MR) imaging features of multiple sclerosis (MS) lesions after the administration of a gadolinium-based contrast agent and ultrasmall superparamagnetic iron oxide (USPIO) particles among the clinical phenotypes of MS and over time. This study was approved by the local ethics committee, and written informed consent was obtained from all patients. Twenty-four patients with MS (10 with relapsing and 14 with progressive forms) underwent clinical and gadolinium- and USPIO-enhanced MR examinations at baseline and 6-month follow-up. The number of lesions that enhanced with gadolinium alone, USPIO alone, or both was compared with the Pearson χ2 or Fisher exact test, and lesion sizes were compared with the Wilcoxon Mann-Whitney U test. At 6-month follow-up, the lesion signal intensity on precontrast T1-weighted images and the enhancement after repeat injection of the contrast agent were compared with the baseline postcontrast imaging features by using the McNemar test. Fifty-six lesions were considered active owing to contrast enhancement at baseline; 37 lesions (66%) in 10 patients enhanced with gadolinium. The use of USPIO helped detect 19 additional lesions (34%), and two additional patients were classified as having active disease. Thus, the use of both agents enabled detection of 51% (19 of 37 lesions) more lesions than with gadolinium alone. Enhanced lesions were more frequently observed in the relapsing compared with the progressive forms of MS (P<.0001). USPIO enhancement, in the form of ringlike patterns, could also be observed on T1-weighted images in patients with progressive MS, enabling the detection of five lesions in addition to the five detected with gadolinium in this phenotype. Lesions that enhanced with both contrast agents at baseline were larger (mean size, 6.5 mm±3.8; P=.001) and were more likely to persistently enhance at 6-month follow-up (seven of 27 lesions, P<.0001) compared with those that enhanced only with gadolinium (mean size, 4.9 mm±2.2; one of nine lesions) or USPIO (mean size, 3.5 mm±1.5; 0 of 17 lesions). The combination of gadolinium and USPIO in patients with MS can help identify additional active lesions compared with the current standard, the gadolinium-only approach, even in progressive forms of MS. Lesions that enhance with both agents may exhibit a more aggressive evolution than those that enhance with only one contrast agent.

CD14 expression and Kupffer cell dysfunction in non‐alcoholic steatohepatitis: Superparamagnetic iron oxide‐magnetic resonance image and pathologic correlation

Kupffer cell (KC) function and CD14 expression contributes to pathogenesis of non-alcoholic steatohepatitis (NASH). However, these relationships remain unclear. We investigated the relationship of KC function with superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), histopathological severity of NASH, and number of CD14-positive KCs in NASH. This retrospective study included 32 patients (24 with NASH and eight with simple steatosis) who had previously undergone SPIO-MRI with T2-weighted gradient-recalled echo sequence. All subjects were diagnosed pathologically and were evaluated for necroinflammation grade, fibrosis stage, and number of CD14-positive KCs. Patients with NASH and simple steatosis were compared by using the Mann-Whitney test to determine differences in percent reduction of liver-to-muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of KC function, and number of CD14-positive KCs. Kruskal-Wallis test and Pearson's correlation coefficient were used to analyze relation among reduction-%LMR, histopathological severity and number of CD14-positive KCs. There were statistically significant differences in reduction-%LMR and number of CD14-positive KCs between NASH and simple steatosis patients (Mann-Whitney test, P < 0.001 for all comparisons). Reduction-%LMR decreased with an increase in necroinflammation grade or fibrosis stage. The number of CD14-positive KCs increased with an increase in necroinflammation grade and fibrosis stage (Kruskal-Wallis test, both, P < 0.001). A high correlation was seen between number of CD14-positive KCs and reduction-%LMR (Pearson r = 0.81; P < 0.001). KC phagocytic function evaluated with SPIO-MRI correlated with histopathological severity and number of CD14-positive KCs. These results support the concept that KC phagocytic dysfunction contributes to the pathogenesis of NASH.

Hypervascular hepatocellular carcinoma in the cirrhotic liver: diffusion-weighted imaging versus superparamagnetic iron oxide-enhanced MRI

Purpose The purpose of the study was to validate diffusion-weighted imaging (DWI) in the assessment of hypervascular hepatocellular carcinoma (HCC) compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the cirrhotic liver. Material and Methods Forty-six consecutive patients with 106 hypervascular focal lesions in the cirrhotic liver who underwent DWI using three b factors and gadopentetate dimeglumine-enhanced dynamic MRI followed by SPIO-enhanced MRI were enrolled. Two independent radiologists evaluated two separated image sets (SPIO set, dynamic MRI and SPIO-enhanced T2*-weighted images; DWI set, DWI and dynamic MRI) and assigned confidence levels for diagnosis of HCC using a five-point scale for each lesion. Area under the receiver operating characteristic curve ( A z) was calculated for each image set. Results The A z value of the DWI set was larger than the SPIO set by both readers (reader 1, 0.936 vs. 0.900, P=.050; reader 2, 0.938 vs. 0.905, P=.110). For the sensitivity (reader 1, 93.1% vs. 86.2%, P=.146; reader 2, 95.4% vs. 88.5%, P=.070) and specificity (reader 1, 89.5% vs. 73.7%, P=.250; reader 2, 79.0% vs. 73.7%, P=1.000) of HCC diagnosis, DWI sets were superior to SPIO sets without statistically significant differences. Conclusion For assessment of hypervascular HCC, DWI in combination with dynamic MRI provides comparable or slightly better information compared with the combination of dynamic and SPIO-enhanced MRI.

Diagnosis of colorectal hepatic metastases: Comparison of contrast‐enhanced CT, contrast‐enhanced US, superparamagnetic iron oxide‐enhanced MRI, and gadoxetic acid‐enhanced MRI

To compare the diagnostic accuracy of contrast-enhanced computed tomography (CE-CT), contrast-enhanced ultrasonography (CE-US), superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), and gadoxetic acid-enhanced MRI (Gd-EOB-MRI) in the evaluation of colorectal hepatic metastases. In all, 111 patients with colorectal cancers were enrolled in this study. Of the 112 metastases identified in 46 patients, 31 in 18 patients were confirmed histologically and the remaining 81 in 28 patients were confirmed by follow-up imaging. CE-CT, CE-US, SPIO-MRI, and Gd-EOB-MRI were evaluated. Mean (of three readers, except for CE-US) area under the receiver operating characteristic curve (A(z) ), sensitivities, and positive predictive values (PPV) were calculated. Each value was compared to the others by variance z-test or chi-square test with Bonferroni correction. For all lesions, mean A(z) and sensitivity of Gd-EOB-MRI (0.992, 95% [56/59]) were significantly greater than those of CE-CT (0.847, 63% [71/112]) and CE-US (0.844, 73% [77/106]). For lesions ≤1 cm, mean A(z) and sensitivity of Gd-EOB-MRI (0.999, 92% [22/24]) were significantly greater than those of CE-CT (0.685, 26% [13/50]) and CE-US (0.7, 41% [18/44]). Mean A(z) (95% CI) of SPIO-MRI for all lesions (0.966 [0.929-0.987]) and lesions ≤ 1 cm (0.961 [0.911-0.988]) were significantly greater than those of CE-CT and CE-US. Mean sensitivity of SPIO-MRI for lesions ≤1 cm (63%, 26/41) was significantly greater than that of CE-CT. Gd-EOB-MRI and SPIO-MRI were more accurate than CE-CT and CE-US for evaluation of liver metastasis in patients with colorectal carcinoma.

Detection of Small Hepatocellular Carcinoma

To investigate whether gadoxetic acid-enhanced magnetic resonance imaging (MRI) has the diagnostic capability and sensitivity comparable to the combination of gadopentetate dimeglumine-enhanced MRI and superparamagnetic iron oxide-enhanced MRI (double-contrast MRI) in the detection of small hepatocellular carcinomas (HCCs). Forty-one patients with 56 HCCs (size range, 0.5-2.0 cm) who underwent gadoxetic acid-enhanced MRI and double-contrast MRI with a mean interval of 4 days (range, 3-9 days) were included in this study. HCCs were diagnosed by histology (n = 25) and imaging findings (n = 31). Two observers independently reviewed the gadoxetic acid set (unenhanced, early dynamic, and hepatocyte phase images) and the double-contrast MRI set, at an initial reading session, and then reached consensus. Diagnostic accuracy and sensitivity were evaluated using the alternative-free response receiver operator characteristic method. Diagnostic accuracy (AZ) and sensitivity were similar for both image sets (0.955, 83.9% for gadoxetic acid set; 0.952, 80.4% for double-contrast MRI set) (P > 0.05). There were 5 and 3 HCCs that were verified only on the gadoxetic acid set and double-contrast MRI set, respectively. All 9 HCCs that were not verified on the gadoxetic acid set were assigned a low confidence rating of 1 or 2. However, 3 of the 11 HCCs, which were not verified on double-contrast MRI, were not seen even upon retrospective review. Gadoxetic acid-enhanced MRI can replace double-contrast MRI for the detection of HCCs. Because all HCCs were delineated on gadoxetic acid-enhanced MRI, even with a low confidence rating, and 3 HCCs were not seen on double-contrast MRI, gadoxetic acid-enhanced MRI could be more advantageous than double-contrast MRI for HCC work-up.

Assessment of liver metastases from colorectal adenocarcinoma following chemotherapy: SPIO-MRI versus FDG-PET/CT

This study compared superparamagnetic iron-oxide-enhanced magnetic resonance imaging (SPIO-MRI) and combined fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in evaluating liver metastases from colorectal adenocarcinoma following chemotherapy. Nineteen patients were included in this retrospective study. SPIO-MRI and PET/CT results were compared with surgery, intraoperative ultrasound and pathology results in 11 patients and with the follow-up in eight patients. SPIO-MRI and PET/CT identified 125 and 71 metastases, respectively. False negative lesions were 11 for SPIO-MRI and 65 for PET/CT. In the whole study population, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 92% and 52% (p<0.001) and the per-segment analysis a sensitivity of 99% and 79% (p<0.001), respectively. In patients who underwent surgery, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 85% and 58% (p<0.05) and the per-segment analysis a sensitivity of 97% and 63% (p<0.05), respectively. In patients who underwent follow-up, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 97% and 47% (p<0.001) and the per-segment analysis a sensitivity of 100% and 63% (p<0.007), respectively. For lesions ≥15 and <30 mm and for lesions <15 mm, SPIO-MRI demonstrated a higher sensitivity than PET/CT (p<0.001). SPIO-MRI appears superior to PET/CT in evaluating liver metastases from colorectal adenocarcinoma following chemotherapy.

Detection of hepatic metastases by superparamagnetic iron oxide-enhanced MR imaging: prospective comparison between 1.5-T and 3.0-T images in the same patients

To prospectively compare the diagnostic performance of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging at 3.0 T and 1.5 T for detection of hepatic metastases. A total of 28 patients (18 men, 10 women; mean age, 61 years) with 80 hepatic metastases were prospectively examined by SPIO-enhanced MR imaging at 3.0 T and 1.5 T. T1-weighted gradient-recalled-echo (GRE) images, T2*-weighted GRE images and T2-weighted fast spin-echo (SE) images were acquired. The tumour-to-liver contrast-to-noise ratio (CNR) of the lesions was calculated. Three observers independently reviewed each image. Image artefacts and overall image quality were analysed, sensitivity and positive predictive value for the detection of hepatic metastases were calculated, and diagnostic accuracy using the receiver-operating characteristics (ROC) method was evaluated. The tumour-to-liver CNRs were significantly higher at 3.0 T. Chemical shift and motion artefact were more severe, and overall image quality was worse on T2-weighted fast SE images at 3.0 T. Overall image quality of the two systems was similar on T1-weighted GRE images and T2*-weighted GRE images. Sensitivity and area under the ROC curve for the 3.0-T image sets were significantly higher. SPIO-enhanced MR imaging at 3.0 T provided better diagnostic performance for detection of hepatic metastases than 1.5 T.

Comparison of gadoxetic acid-enhanced MRI and superparamagnetic iron oxide-enhanced MRI for the detection of hepatocellular carcinoma

To compare the diagnostic accuracy and sensitivity of gadoxetic acid-enhanced MRI and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC). Eighty-nine patients (118 HCCs) who underwent three-dimensional gadoxetic acid-enhanced MRI and SPIO-enhanced MRI with a mean interval of 4.7 days (range 3-7 days), were included in this study. Two observers reviewed the gadoxetic acid set (unenhanced, early dynamic, 10 and 20 min hepatocyte-phase images) and SPIO set [unenhanced and ferucarbotran-enhanced T1-, T2-turbo spin-echo (TSE), and T2* weighted imaging (WI)] in consensus. Diagnostic accuracy and sensitivity were evaluated using the alternative-free response receiver operator characteristic (ROC) method. The area under ROC curve (Az value) and sensitivity of the gadoxetic acid set (Az 0.964; sensitivity 90.7%) were significantly higher than those of the SPIO set (Az 0.830; sensitivity 84.7%; p<0.05). There were 14 and seven lesions that were verified only on the gadoxetic acid set and only on the SPIO set, respectively. Four HCCs were clearly revealed as hypointense only on gadoxetic acid-enhanced hepatocyte phase imaging, but were occult on other sequences, including the SPIO set. Gadoxetic acid-enhanced MRI is better than SPIO-enhanced MRI for the detection of HCCs.

Detection and Characterization of Focal Liver Lesions

To prospectively evaluate the safety and efficacy of combined unenhanced and gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging compared with unenhanced MR imaging and triphasic contrast-enhanced spiral computed tomography (CT) for the detection and characterization of focal liver lesions. The study was reviewed and approved by the institutional review board at each of the 15 centers involved in the study, and informed written consent was given by all patients. In total, 178 patients with suspected focal hepatic lesions (based, in most patients, on CT, tumor marker and ultrasound examinations) underwent combined MR imaging with a single, rapid injection of Gd-EOB-DTPA 0.025 mmol/kg, including T1-weighted dynamic and delayed MR images 20 to 40 minutes postinjection. Triphasic contrast-enhanced CT, the comparator examination, was performed within 4 weeks of MR imaging. Standard of references (SOR) were resection histopathology and intraoperative ultrasonography, or combined CT during arterial portography and CT hepatic arteriography; in cases where, although the major lesions were treated, some lesion(s) were not treated, follow-up superparamagnetic iron oxide-enhanced MR imaging was additionally performed. All images were assessed for differences in lesion detection and characterization (specific lesion type) by on-site readers and 3, blinded (off-site) reviewers. All adverse events (AEs) occurring within 72 hours after Gd-EOB-DTPA administration were reported. Overall, 9.6% of patients who received Gd-EOB-DTPA reported 21 drug-related AEs. A total of 151 patients were included in the efficacy analysis. Combined MR imaging showed statistically higher sensitivity in lesion detection (67.5%-79.5%) than unenhanced MR imaging (46.5%-59.1%; P < 0.05 for all). Combined MR imaging also showed higher sensitivity in lesion detection than CT (61.1%-73.0%), with the results being statistically significant (P < 0.05) for on-site readers and 2 of 3 blinded readers. Higher sensitivity in lesion detection with combined MR imaging compared with CT was also clearly demonstrated in the following subgroups: lesions with a diameter <or=20 mm (lesions <or=10 mm: 38.0%-55.4% vs. 26.1%-47.3%, respectively; lesions 10-20 mm: 71.1%-87.3% vs. 65.7%-78.4%, respectively); in cirrhotic patients (64.5%-75.4% vs. 54.5%-70.3%, respectively); and in patients with hepatocellular carcinoma (66.6%-78.6% vs. 59.1%-71.6%, respectively). Combined MR imaging demonstrated a higher proportion of correctly characterized lesions (50.5%-72.1%) than unenhanced MR imaging (30.2%-50.0%; P < 0.05 for all), whereas there were no significant differences compared with CT (49.0%-68.1%), except for one blinded reader (P < 0.05). In this study, hepatocyte-specific Gd-EOB-DTPA was shown to be safe and to improve the detection and characterization of focal hepatic lesions compared with unenhanced MR imaging. When compared with spiral CT, Gd-EOB-DTPA enhanced MRI seems to be beneficial especially for the detection for smaller lesions or hepatocellular carcinoma underlying cirrhotic liver.

SPIO Enhanced MR Imaging for the Detection of Metastases in Sentinel Nodes Localized by CT Lymphography in Patients with Breast Cancer.

Abstract Background: Ultrasonography, magnetic resonance (MR) imaging, and computed tomography (CT) may detect nodal metastases in patients with breast cancer, but there is not sufficient accuracy with the conventional methods. Recently, superparamagnetic nanoparticles-enhanced MR imaging has been reported to be a promising improvement for diagnostic imaging of lymph node metastases from various tumors. Moreover, sentinel nodes have been reported to be well-identified using CT lymphography in patients with breast cancer. This study evaluated MR imaging with superparamagnetic iron oxide (SPIO) enhancement for the detection of metastases in sentinel nodes localized by CT lymphography in patients with breast cancer, with histopathologic findings as the reference standard.Methods: This study included 102 patients with breast cancer with clinically negative nodes. Each contrast agent was injected intradermally into the skin overlying the breast tumor and in the subareolar region. Sentinel nodes were identified by CT lymphography, and SPIO-enhanced MR imaging of the axilla was performed to detect metastases in the sentinel nodes. 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 node biopsy was performed using a combination of dye and radiocolloid. Imaging results were correlated with histopathologic findings.Results: The mean number of sentinel nodes identified by CT lymphography was 1.1 (range 1–3). Twenty-one of 25 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Seventy of 77 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity, and overall accuracy of MR imaging for the diagnosis of sentinel node metastases were 84%, 91%, and 89%, respectively. In four of 10 patients with micrometastases, the metastases were not detected, but all 15 patients with macrometastases were successfully demonstrated. There were no adverse events associated with either CT or MR imaging.Conclusions: SPIO-enhanced MR imaging is a useful method of detecting metastases in sentinel nodes localized by CT lymphography in patients with breast cancer. Patients with clinically negative nodes may be spared sentinel node biopsy when the sentinel node is diagnosed as disease-free using SPIO-enhanced MR imaging. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1010.

Detection of Hepatic Metastases From Colorectal Carcinoma

The specificity and sensitivity of intravenous-enhanced multidetector row computed tomography (MDCT), superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), multidetector row computed tomography with arterioportography combined with multidetector row computed tomography with hepatic arteriography (CTAP/CTHA), and intraoperative ultrasonography (IOUS) for detecting hepatic metastases from colorectal carcinoma were evaluated based on histopathologic examination of resected livers. MDCT, SPIO-MRI, CTAP/CTHA, and IOUS were performed routinely to determine surgical indications and methods in patients with hepatic metastases from colorectal carcinoma. The resected liver specimens were then cut serially into sections 3 to 5 mm thick for routine histologic examination. Fifty metastatic lesions were detected by histopathologic study of a large amount of anatomically resected liver from 8 patients with colorectal liver metastasis. The tumors ranged in size from 3 to 53 mm (mean 13.8 mm) and 26 lesions (52%) were less than 10 mm in diameter. Histopathologic examination of the resected liver specimens showed that CTAP/CTHA was the most sensitive imaging modality, followed in order by IOUS, SPIO-MRI, and MDCT. Among all the tumors detected by CTAP/CTHA, SPIO-MRI overlooked 5, but all of the tumors detected by SPIO-MRI were also detected by CTAP/CTHA. The number of metastatic liver tumors detected differed significantly among MDCT, SPIO-MRI, and histopathologic examination. One false-positive lesion was detected by IOUS. CTAP/CTHA is a useful preoperative imaging modality for detecting small hepatic metastases from colorectal carcinoma.

Lymph Node Metastasis: Ultrasmall Superparamagnetic Iron Oxide–enhanced MR Imaging versus PET/CT in a Rabbit Model

To prospectively compare the diagnostic accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging and integrated positron emission tomography-computed tomography (PET/CT) for the depiction of lymph node metastasis in an animal model, with histologic findings as the reference standard. This experiment was approved by the local animal care committee. VX2 carcinoma was implanted into the thighs of 11 rabbits 4 weeks before the imaging study. T2- and T2*-weighted MR examinations were performed 24 hours after USPIO administration, followed by integrated PET/CT. USPIO-enhanced MR imaging and PET/CT analysis for the evaluation of the presence of metastasis in iliac lymph nodes were performed independently by two radiologists and two nuclear medicine physicians, respectively, without histopathologic knowledge. Results were evaluated by using receiver operating characteristic (ROC) analysis, and sensitivities and specificities were compared by using a Z test. Metastases were histopathologically confirmed in 22 of 62 iliac lymph nodes. USPIO-enhanced MR imaging showed a significantly greater area under the ROC curve than did PET/CT (0.984 vs 0.852; P=.023). The respective sensitivity and specificity for the detection of lymph node metastasis were 91% (20 of 22) and 95% (38 of 40) for USPIO-enhanced MR imaging and 64% (14 of 22) and 98% (39 of 40) for PET/CT. In terms of sensitivity, a significant difference was found between USPIO-enhanced MR imaging and PET/CT, particularly for nodal metastasis of less than 5 mm (86% [six of seven] vs 0% [zero of seven]; P=.031), whereas the specificity of the two imaging modalities was similar (P=.226). USPIO-enhanced MR imaging results in higher diagnostic accuracy for depicting lymph node metastasis than does PET/CT.

Multidetector helical CT plus superparamagnetic iron oxide-enhanced MR imaging for focal hepatic lesions in cirrhotic liver: A comparison with multi-phase CT during hepatic arteriography

The aim of this study was to evaluate multidetector helical computed tomography (MDCT), superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging, and CT arterial portography (CTAP) and CT during hepatic arteriography (CTHA) for the detection and diagnosis of hepatocellular carcinomas (HCC). This included visual correlations of MDCT and SPIO-MR imaging in the detection of HCC using receiver operating characteristic (ROC) analysis. Twenty-five patients with 57 nodular HCCs were retrospectively analyzed. A total of 200 segments, including 49 segments with 57 HCCs, were reviewed independently by three observers. Each observer read four sets of images (set 1, MDCT; set 2, unenhanced and SPIO-enhanced MR images; set 3, combined MDCT and SPIO-enhanced MR images; set 4, combined CTAP and CTHA). The mean Az values representing the diagnostic accuracy for HCCs of sets 1, 2, 3, and 4 were 0.777, 0.814, 0.849, and 0.911, respectively, and there was no significant difference between sets 3 and 4. The sensitivity of set 4 was significantly higher than those of set 3 for all the lesions and for lesions 10 mm or smaller ( p < 0.05); however, for lesions larger than 10 mm, the sensitivities of the two sets were similar. No significant difference in positive predictive value and specificity was observed between set 3 and set 4. Combined MDCT and SPIO-enhanced MR imaging may obviate the need for more invasive CTAP and CTHA for the pre-therapeutic evaluation of patients with HCC more than 10 mm.

Ultrasmall Superparamagnetic Iron-Oxide–enhanced MR Imaging of Normal Bone Marrow in Rodents: Original Research: Original Research 1

The objective is to compare three different ultrasmall superparamagnetic iron oxides (USPIOs) for magnetic resonance (MR) imaging of normal bone marrow in rodents. Femoral bone marrow in 18 Sprague-Dawley rats was examined by using MR imaging before and up to 2 and 24 hours postinjection (PI) of 200 mumol of Fe/kg of SHU555C (n = 6), ferumoxtran-10 (n = 6), or ferumoxytol (n = 6), using T1-weighted (50 ms/1.7 ms/60 degrees = repetition time [TR]/echo time [TE]/flip angle) and T2*-weighted (100 ms/15 ms/38 degrees = TR/TE/flip angle) three-dimensional spoiled gradient recalled echo sequences. USPIO-induced bone marrow was evaluated qualitatively and quantified as signal-to-noise ratio (SNR) and change in signal intensity (DeltaSI) values. A mixed-effect model was fitted to the SNR and DeltaSI values, and differences among USPIOs were tested for significance by using F tests. At 2 hours PI, all three USPIOs showed marked positive signal enhancement on T1-weighted images and a corresponding marked signal loss on T2*-weighted images. At 24 hours PI, the T1 effect of all three USPIOs disappeared, whereas T2*-weighted images showed persistent signal loss on SHU555C and ferumoxytol-enhanced MR images, but not ferumoxtran-10-enhanced MR images. Corresponding SNR and DeltaSI values on T2*-weighted MR images at 24 hours PI were significantly different from baseline for SHU555C and ferumoxytol, but not ferumoxtran-10. All three USPIO contrast agents, ferumoxtran-10, ferumoxytol, and SHU555C, can be applied for MR imaging of bone marrow. Ferumoxtran-10 apparently reveals a different kinetic behavior in bone marrow than ferumoxytol and SHU555C.

Superparamagnetic iron oxide-enhanced MR imaging for focal hepatic lesions: a comparison with CT during arterioportography plus CT during hepatic arteriography

We aimed to evaluate the efficacy of a breath-hold superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging protocol for the detection of focal hepatic lesions, in comparison with a non-breath-hold SPIO-enhanced imaging protocol and computed tomography during arterioportography (CTAP) plus CT during hepatic arteriography (CTHA). Findings of SPIO-enhanced MR imaging and CTAP/CTHA for 24 hepatic metastases in 17 patients and 29 HCCs in 21 patients were analyzed. All patients underwent breath-hold SPIO-enhanced MR imaging (1.5 tesla), breath-hold plus non-breath-hold SPIO-enhanced MR imaging, and CTAP plus CTHA prior to partial hepatectomy or laparoscopic ablation therapy. Histopathology for lesion characterization and intraoperative ultrasound for lesion detection were available for all patient. Breath-hold SPIO-enhanced MR imaging consisted of T2-weighted single-short fast spin echo (FSE), T2-weighted (T2W) FSE, T2*-weighted gradient echo (GRE), and T1-weighted GRE. For the non-breath-hold imaging protocol, respiratory-triggered, fat-suppressed T2W-FSE was added to the breath-hold MR imaging protocol. Double phase CTAP plus CTHA was performed on an angio-CT system. To compare the three imaging protocols, three radiologists performed blind film reading, and all data, on a hepatic segment-to-segment basis, were entered for alternative free-response receiver-operating characteristic (AFROC) analysis. ROC analysis showed that there was no significant difference in the area under the AFROC curve (A1) value for metastases and HCCs among the three protocols; the breath-hold SPIO-enhanced MR imaging protocol, non-breath-hold MR imaging protocol, and CTAP plus CTHA. The breath-hold SPIO-enhanced MR imaging protocol showed a sensitivity, specificity, and accuracy equivalent to the non-breath-hold MR imaging protocol and CTAP plus CTHA. As a preoperative test, SPIO-enhanced MR imaging could have the potential to replace CTAP plus CTHA in a certain clinical setting.

SPIO-MRIにおけるFRFSE法の有用性

Super-paramagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) is highly sensitive for liver tumors. This trial examined the optimal parameters of the fast recovery fast spin echo (FRFSE) method in SPIO-MRI. The FRFSE method is a pulse sequence with recovery of the compulsory longitudinal magnetization. The FRFSE method used in SPIO-MRI has better sensitivity for liver tumor, better tumor contrast, and can be used with respiratory gating. The phantoms used included a ferucarbotran phantom, water phantom, and gelatin phantom. Each phantom was scanned by the FRFSE method and fast spin echo (FSE) method, with changing of scanning parameters, and each CNR was measured. Each CNR was given a point, and points were averaged according to each parameter. Parameters that obtained high average points were considered optimal parameters. The optimal parameters were set to TE=50 ms in the FRFSE method. The scan parameters optimized from the phantom study were used in a clinical case, and good results were achieved, as in the phantom study. We optimized the scan parameters of the FRFSE method and were able to suggest the usefulness of the FRFSE method in SPIO-MRI.