Superparamagnetic Iron Oxide-enhanced Magnetic Resonance Research Articles

M1128 Prospective Study to Detect Metastases of the Liver By Using Contrast Enhanced Ultrasound: Comparison with Multi-Detector Row Computed Tomography and Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging

M1128 Prospective Study to Detect Metastases of the Liver By Using Contrast Enhanced Ultrasound: Comparison with Multi-Detector Row Computed Tomography and Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging

Comparative study of images with pathology: Superparamagnetic iron oxide-enhanced magnetic resonance image (MRI) of splenic VX2 tumor in rats

To establish a rodent model of VX2 tumor of the spleen, to analyze relationship between the change of the signal intensity on superparamagnetic iron oxide enhanced magnetic resonance image (MRI) and pathologic change to evaluate the ability of superparamagnetic iron oxide enhanced MRI for detection of splenic metastases. 8 rodent models of VX2 tumor of spleen were established successfully. The images were obtained before and after administration of superparamagnetic iron oxide. T1-weighted spin-echo (SE) pulse sequence with a repetition time (TR) of 450 msec, and echo time (TE) of 12 msec (TR/TE=450/12) was used. The imaging parameters of T2-weighted SE pulse sequence were as follows: TR/TE=4000/128. On plain MR scanning T1-weighted splenic VX2 tumor showed hypointensity or isointensity which approximated to the SI of splenic parenchyma. Therefore all lesions were not displayed clearly. On superparamagnetic iron oxide enhancement T2WI sequence the SI of splenic parenchyma decreased obviously with percentage of signal intensity loss (PSIL) of 55.04%, But the SI of tumor was not evidently changed with PSIL of 0.87%. Nevertheless the SNR of normal splenic parenchyma around the lesions had obvious difference (P<0.001) comparatively. Therefore the contrast between tumor and spleen increased, and tumor displayed more clearly. Moreover the contrast-to-noise (CNR) between VX2 tumor and splenic parenchyma had an evident difference before and after admininstration of superparamagnetic iron oxide (P<0.001). On superparamagnetic iron oxide enhancement T1WI sequence the contrast of tumor-to-spleen is poor. Therefore it is not sensitive to characterize the lesions in spleen. On superparamagnetic iron oxide enhanced T2WI the contrast degree of lesions increases obviously. Consequently, superparamagnetic iron oxide-enhanced T2WI MRI scanning can improve the rate of detection and characterization for lesions of spleen.

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.

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.

Laparoscopic extirpation of splenic hamartoma

We presented a case of splenic hamartoma. A 12-year-old girl has had an abdominal pain since 9 years of age. Contrast-enhanced computed tomography scan at a local hospital revealed heterogeneous enhancement of a mass which is 5 cm in diameter, located near the surface of the spleen, diagnosed as hemangioma. She had an investigation with Levovist-enhanced ultrasonography and superparamagnetic iron oxide-enhanced magnetic resonance imaging on T2-weighted gradient-echo imaging, which showed a hypervascular echoic mass and a decrease of signal intensity. The imaging diagnosis was splenic hamartoma. She underwent laparoscopic splenectomy to prevent the spontaneous rupture. The splenic artery at the pancreas body was exposed, and doubly ligated by vessel clip and furthermore ligated by 3-0 silk. At the splenic hilum, the splenic artery and vein were dissected with the Endo GIA vascular linear cutting stapler. The spleen was captured into the Endocatch II retrieval bag and removed from a transverse lower abdominal (suprapubic) incision extended up 7 cm in length through a port site. In pathological findings, the tumor was compatible with hamartoma. Splenic hamartomas in pediatric patients have been described extremely rare. In clinical symptoms, spontaneously ruptured splenic hamartoma has been rarely reported.

Metalloproteinases Control Brain Inflammation Induced by Pertussis Toxin in Mice Overexpressing the Chemokine CCL2 in the Central Nervous System

Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation. This involves cellular migration across various structures associated with the blood-brain barrier: the vascular endothelium, the glia limitans, and the perivascular space between them. Leukocytes accumulate spontaneously in the perivascular space in brains of transgenic (Tg) mice that overexpress CCL2 under control of a CNS-specific promoter. The Tg mice show no clinical symptoms, even though leukocytes have crossed the endothelial basement membrane. Pertussis toxin (PTx) given i.p. induced encephalopathy and weight loss in Tg mice. We used flow cytometry, ultra-small superparamagnetic iron oxide-enhanced magnetic resonance imaging, and immunofluorescent staining to show that encephalopathy involved leukocyte migration across the glia limitans into the brain parenchyma, identifying this as the critical step in inducing clinical symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor of metalloproteinase-1, metalloproteinase disintegrins-12, MMP-8, and -10 in brains of Tg mice. Levels of the microglial-associated MP MMP-15 were not affected in control or PTx-treated Tg mice. PTx also up-regulated expression of proinflammatory cytokines IL-1beta and TNF-alpha mRNA in Tg CNS. Weight loss and parenchymal infiltration, but not perivascular accumulation, were significantly inhibited by the broad-spectrum MP inhibitor BB-94/Batimastat. Our finding that MPs mediate PTx-induced parenchymal infiltration to the chemokine-overexpressing CNS has relevance for the pathogenesis of human diseases involving CNS inflammation, such as multiple sclerosis.

Accuracy of preoperative prediction of microinvasion of portal vein in hepatocellular carcinoma using superparamagnetic iron oxide-enhanced magnetic resonance imaging and computed tomography during hepatic angiography

Our aim was to diagnose microinvasion of the portal vein in hepatocellular carcinoma from preoperative radiological findings and to construct a scoring system. Forty-seven patients (38 men and 9 women; median age, 66.8 years) who underwent hepatic resections for hepatocellular carcinoma were selected retrospectively. Microscopically, 22 had portal vein invasion (PVI) and 25 had no PVI. All patients were examined preoperatively with superparamagnetic iron oxide-enhanced magnetic resonance imaging and computed tomography during hepatic angiography (CTHA). Perilesional enhancement on T1-weighted imaging, tumorous arterioportal (AP) shunt, and corona enhancement (contrast enhancement of the adjacent liver appearing in the late phase of CTHA) were assessed. Relative risk for PVI in terms of clinical and tumor characteristics was also assessed. The relative contribution to PVI was determined by the coefficient of a stepwise logistic regression. Each variable was given a score relative to the coefficient. On univariate analysis, distortion of corona, tumorous AP shunt, and tumor size indicated a higher prevalence of PVI. The PVI predictive score was calculated as: total score = (maximum size in cm) + (T1 ring; + = 1, - = 0) + (tumorous AP shunt; + = 3, - = 0) + (distortion of corona; + = 10, - = 0). The PVI (+) group score was four times that of the PVI (-) group (16 vs 4). At a cutoff score of 10, the sensitivity, specificity, and accuracy were 82%, 84%, and 86%. Distortion of corona, tumorous AP shunt, and tumor size are good predictors of the risk of PVI. This scoring system is simple and worth using clinically.

Detection and characterization of liver metastases: 16--slice multidetector computed tomography versus superparamagnetic iron oxide-enhanced magnetic resonance imaging

The aim of our study was to compare the diagnostic performance of 16--slice multidetector computed tomography with that of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging in the detection of small hepatic metastases and in the differentiation of hepatic metastases from cysts. Twenty-three patients with 55 liver metastases and 14 liver cysts underwent SPIO-enhanced MR imaging and multiphasic CT using 16-MDCT. Two observers independently analyzed each image, in random order. Sensitivity and diagnostic accuracy for lesion detection and differentiation as metastases or cysts for MDCT and SPIO-enhanced MR imaging were calculated using receiver operating characteristic analysis. For all observers, the Az values of SPIO-enhanced MR imaging for lesion detection and differentiation of liver metastases from cysts (mean 0.955, 0.999) were higher than those of MDCT (mean 0.925, 0.982), but not statistically significantly so (P > 0.05). Sensitivity of SPIO-enhanced MR imaging with regard to the detection of liver metastases (mean 94.5%) was significantly higher than that of MDCT (mean 80.0%) (P < 0.05). SPIO-enhanced MR imaging and 16-MDCT showed similar diagnostic accuracies for detection and differentiation of liver metastases from cysts, but sensitivity of SPIO-enhanced imaging in the detection of liver metastases was superior to that of 16-MDCT.

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.

Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging.

To examine the efficacy of FTY720 as a new agent to reduce inflammatory activity in an animal model of multiple sclerosis (MS) by in vivo macrophage tracking. FTY720 was used for treatment of rats in a model of chronic relapsing experimental autoimmune encephalomyelitis (EAE) at an oral dose of 0.3 mg/kg/day. Magnetic resonance imaging (MRI) based on in vivo tracking of macrophages labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, immunohistological staining (IHC), and neurological readouts was used to study the burden of disease in treated and untreated animals. While untreated animals showed severe paralysis of the hind paws, intense accumulation of macrophages in brain tissue, and areas of blood-brain barrier (BBB) disruption, FTY720-treated animals displayed no signs of inflammatory activity or neurological impairment. These observations were made for both acute phase and first relapse. Tracking of macrophages by MRI provides direct evidence of the immunomodulatory efficacy of FTY720 in the EAE model and correlates well with neurological symptoms and histology.

Efficacy of SPIO-MR Imaging in the Diagnosis of Liver Metastases from Colorectal Carcinomas

Aim: To determine whether superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) could replace intravenous contrast-enhanced spiral CT (iv-CT) and spiral CT during arterial portography (CTAP) combined with spiral CT hepatic angiography (CTHA) in the diagnosis of liver metastases from colorectal carcinomas. Methods: Twenty-six adult patients with liver metastases were studied preoperatively by means of iv-CT, CTAP/CTHA, and SPIO-MRI. Preoperative diagnoses using iv-CT, CTAP/CTHA, and SPIO-MRI were compared with intraoperative and pathological findings in resected specimens. The gold standard for the lesions that were resected was histological examination. Intraoperative findings represented the gold standard for lesions that were not resected. Results: Twenty-six patients were found to have a total number of 43 liver metastases. The sensitivities of iv-CT, CTAP/CTHA, and SPIO-MRI were 74.4, 100, and 90.7%, respectively. SPIO-MRI was significantly superior to iv-CT (p < 0.05). The positive predictive values of iv-CT, CTAP/CTHA, and SPIO-MRI were 97.0, 91.5, and 100%, respectively. CTAP/CTHA yielded four false-positive lesions. In contrast, we detected no false-positive findings using SPIO-MRI. Conclusions: These results suggest that SPIO-MRI might not completely replace CTAP/CTHA, but could replace iv-CT in the diagnosis of liver metastases from colorectal carcinomas. It is thought that SPIO-MRI is a promising imaging modality for diagnosing liver metastases in patients with colorectal carcinoma because of its relatively high sensitivity and extremely high specificity.

Superparamagnetic iron oxide-enhanced magnetic resonance imaging of the liver in beagle dogs.

The role of superparamagnetic iron oxide as a tissue-specific contrast medium has been established in humans, especially for hepatic imaging. Superparamagnetic iron oxide particles exhibit a tissue-specific biodistribution to the reticuloendothelial system, where they predominantly shorten transverse T2 relaxation time. Most hepatic tumors lack Kupffer cells; therefore, the T2 of tumors remains virtually unchanged after administration of superparamagnetic iron oxide. The resulting loss of signal intensity from the liver, with unchanged tumor signal intensity, increases lesion-to-liver contrast. In this study, MR images were acquired with fast gradient echo recalled at steady state (FGRE) in five Beagle dogs before and after injection of superparamagnetic iron oxide. The effect of superparamagnetic iron oxide on signal intensity of the liver with time was assessed. A signal intensity decrease of 65.7+/-10.0% was detected at 20 minutes, and it continued to decrease until the last time point of MR scanning (200 minutes). The liver intensity of all dogs dropped to half its value after 20 minutes. The effect of motion was minimized by breath holding. Superparamagnetic iron oxide did not have any adverse effects on the dogs.

Superparamagnetic iron oxide-enhanced magnetic resonance imaging is a beneficial modality for early diagnosis of hepatocellular carcinoma. A comparison with the vascular characterization by CT arteriography and CT arterioportography

Superparamagnetic iron oxide-enhanced magnetic resonance imaging is a beneficial modality for early diagnosis of hepatocellular carcinoma. A comparison with the vascular characterization by CT arteriography and CT arterioportography

Development of hepatomas in hyperplastic nodules induced in the rat liver: detection with superparamagnetic iron oxide-enhanced magnetic resonance imaging.

Hyperplastic nodules developed in cirrhotic livers reportedly show accumulations of superparamagnetic iron oxide (SPIO) on magnetic resonance (MR) images, whereas hepatocellular carcinomas do not. We examined whether SPIO-enhanced MR imaging would detect cancerous liver lesions within hyperplastic nodules. The study included 40 rats with N-2-fluorenyldiacetamide (FAA)-induced liver tumors. Spin-echo T1-, T2-, and proton density-weighted images were obtained at 1.5 T before and after the administration of SPIO. We evaluated 47 tumors accumulating iron particles on SPIO-enhanced MR images. Among the 47 tumors, 33 were observed on MR images obtained 10-26 weeks after the initiation of the carcinogenic diet. The signal intensity changes within the tumors were observed at 2 weeks and were compared with histologic findings. As a control study, 30 hyperintense (non-SPIO-enhanced) tumors also received pathologic examination. Hyperintense (non-SPIO-enhanced) foci within hypointense (SPIO-enhanced) tumors were observed in seven of the 33 tumors on all pulse sequences, and hyperintense (non-SPIO-enhanced), enlarged foci were observed in three of the seven lesions. In the remaining 26 lesions, the signal intensity of the tumor was totally hypointense on all pulse sequences at initial and follow-up MR imaging. During the 2-week follow-up period, 15 hypointense (SPIO-enhanced) tumors were replaced by hyperintense (non-SPIO-enhanced) tumors. Histologically, SPIO-accumulating tumors were hyperplastic nodules; the lesions that did not accumulate SPIO were hepatocellular carcinomas or hyperplastic nodules with atypical cells. MR imaging using SPIO detects the development of hepatocellular carcinoma at an early stage in our animal model.

Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging of Experimental Liver Tumors after Mitomycin C Administration

The influence of mitomycin C chemotherapy on superparamagnetic iron oxide (SPIO) uptake by the liver was studied in rats (n = 70). This commonly used antineoplastic drug induces a decrease in the phagocytic function of the macrophage-phagocytic system (MPS). The plasma clearance of SPIO measured by relaxometry followed a biexponential model. The fast component half-life increased from 2.9 minutes in controls to 4.5 minutes in mitomycin C-treated animals. The slow component half-life increased from 11.3 to 36.7 minutes. Nevertheless, the magnetic resonance imaging (MRI) diagnostic efficacy 2 hours after infusion of the superparamagnetic agent AMI 25 (n = 10) was as satisfactory in the treated group as in the untreated one. These MRI results were consistent with the relaxometric T2* liver measurements, which were identical in both groups.