Ultrasmall supraparamagnetic iron oxide-enhanced magnetic resonance imaging of antigen-induced arthritis: a comparative study between SHU 555 C, ferumoxtran-10, and ferumoxytol

OBJECTIVES: We sought to compare the ability of 3 ultrasmall superparamagnetic iron oxides (USPIOs) to detect and characterize antigen-induced arthritis with MR imaging. MATERIALS AND METHODS: A monoarthritis was induced in the right knee of 18 rats. The left knee served as a normal control. Knees underwent magnetic resonance (MR) imaging before, up to 2 hours, and 24 hours after injection (p.i.) of 200 mumol Fe/kg SHU 555 C (n= 6), ferumoxtran-10 (n = 6), or ferumoxytol (n = 6), using T2-2D-SE 100/20,40,60,80/90 (TR/TE/flipangle), T2*-3D-spoiled gradient recalled (SPGR) 100/15/38, and T1-3D-SPGR 50/1,7/60 sequences. RESULTS: Quantitative signal to noise ratio and DeltaSI data of arthritic knees on T1- and T2*-weighted MR images showed no significant differences between the 3 USPIOs (P > 0.05). At 2 hours p.i., SNR and DeltaSI data were significantly increased from baseline on T1-weighted images and significantly decreased on T2*-weighted images (P < 0.001). At 24 hours p.i., the T1-enhancement returned to baseline, whereas the T2*-enhancement remained significantly elevated (P < 0.001). Immunostains demonstrated an USPIO compartmentalization in macrophages in the arthritic synovium. CONCLUSIONS: Based on the relatively small number of animals in our study group, inflammation in antigen-induced arthritis can be equally detected and characterized with any of the three USPIOs evaluated.     

RES-specific imaging of the liver and spleen with iron oxide particles designed for blood pool MR-angiography.

The purpose of this study was to determine the dependency of liver- and spleen-enhancement on particle size and dose of bolus-injectable iron oxides designed for blood-pool MR-angiography (MRA). The superparamagnetic iron oxide SHU 555 A [particle size 65 nm (group 1)] and three derivatives designed for blood-pool MRA (groups 2-4) with smaller hydrodynamic diameters (46/33/21 nm) were i.v. injected in New Zealand White rabbits at doses of 10, 20, or 40 micromol Fe/kg bw. MRI was performed before, 2, and 24 hours after contrast application using T1-weighted SE and T2-weighted TSE sequences. In addition splenic tissue was harvested post mortem and scanned ex vivo. All iron oxides significantly decreased the SI of liver and spleen in T1- and T2-weighted images at 2 and 24 hours after application of contrast media (P < 0.01). The signal intensity was inversely related to the dose applied. Decreasing particle size resulted in a lower signal enhancement in liver and spleen. However, ultra-small superparamagnetic iron oxides suited for blood-pool MRA (USPIOs, group 4) still revealed a significant signal enhancement in the liver and spleen even 24 hours after contrast application (< - 60%, 40 micromol Fe/kg bw). They might thus be used for comprehensive abdominal studies including contrast enhanced MR-angiography and RES-specific imaging.     

MR imaging with ultrasmall superparamagnetic iron oxide particles in experimental soft-tissue infections in rats

PURPOSE: To investigate the feasibility of macrophage magnetic resonance (MR) imaging in rats by using an experimental soft-tissue infection model. MATERIALS AND METHODS: Thirteen rats with unilateral calf-muscle infection were imaged with a 4.7-T MR imager at an early chronic stage of infection (day 4 before contrast material injection, days 4-7 after injection). Eleven animals were imaged before and 3 and 24 hours after intravenous application of ultrasmall superparamagnetic iron oxide (USPIO), and eight animals were additionally imaged 48 hours and three animals 72 hours after USPIO application. Two infected rats served as controls. T1- and T2-weighted spin-echo and T2*-weighted gradient-echo sequences were applied. All animals were sacrificed, and histopathologic findings were correlated with findings on MR images. Electron microscopy was performed in two rats. For quantitative analysis, signal intensities on T2*-weighted images and T2 values on T2 maps were measured within regions of interest, and the temporal variation was analyzed by using the signed rank test. RESULTS: Visualization of USPIO-loaded macrophages was most sensitive with a T2*-weighted sequence. USPIO distribution pattern and quantitative analysis of T2 and T2* effects 3 hours after USPIO application were significantly different (P <.05) from those at 24 and 48 hours, reflecting the dynamic transit of the particle accumulation from the intravascular to the intracellular compartment by means of macrophage phagocytosis. Local signal intensity alterations could be correlated with iron-loaded macrophages at histopathologic examination. CONCLUSION: Activated macrophages in acute soft-tissue infection can be labeled with USPIOs and detected with MR imaging because of susceptibility effects.     

Differential uptake of ferumoxtran-10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: critical determinants of atherosclerotic plaque labeling

PURPOSE: To compare atherosclerotic plaque uptake of a first (ferumoxtran-10) and second generation (ferumoxytol) ultrasmall superparamagnetic iron oxide (USPIO) contrast agent with different pharmacokinetic/pharmacodynamic properties. MATERIALS AND METHODS: New Zealand White rabbits maintained on a high cholesterol/fat diet were subjected to balloon injury to the abdominal aorta. Ferumoxtran-10 or ferumoxytol (500 micromol/kg) was administered at 2, 4, and 8 weeks following injury. In vivo magnetic resonance imaging (MRI) was performed immediately prior to, immediately after, and 6 days post-contrast administration. Ex vivo MRI, histologic, and inductively coupled plasma-mass spectrometry (ICP-MS) iron analyses were performed on the excised vessels. RESULTS: The blood pool clearance of ferumoxytol (t(1/2) < or = 6 hours) was more rapid than that of ferumoxtran-10 (t(1/2) < or = 48 hours). Decreased in vivo MRI signal intensity in the abdominal aorta was observed at 2, 4, and 8 weeks following injury with ferumoxtran-10, but not with ferumoxytol. Consistent with these observations, ex vivo MRI signal intensity was decreased in the ferumoxtran-10 vessels, and to a lesser degree in the ferumoxytol vs. control vessels (- contrast agent). In contrast, in vitro macrophage phagocytosis of USPIO was four to six fold greater with ferumoxytol than with ferumoxtran-10. Additionally, the absolute iron content correlated with ex vivo MRI signal intensity in all vessels (r = -0.86, P < 0.0001). CONCLUSIONS: These data suggest that the exposure period of atherosclerotic plaque to USPIO rather than the kinetics of the USPIO uptake by plaque alone is a critical criterion for experimental design of in vivo studies.     

Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide

PURPOSE: To evaluate a new ultrasmall superparamagnetic particles of iron oxide (USPIO) compound, ferumoxytol, as a marker of macrophage activity in atherosclerotic plaques and to compare it to ferumoxtran-10. MATERIALS AND METHODS: Ten mature heritable hyperlipidemic (WHHL) female Watanabe rabbits served as the animal model for atherosclerosis, four coeval female New Zealand White (NZW) rabbits were the control group. Five WHHL and two NZW received a single intravenous injection (250 micromol/kg) of either ferumoxtran-10 or ferumoxytol and were subjected to daily MR examinations on a 1.5T whole body scanner for the next five days. Development of signal intensity changes and susceptibility effects was assessed. Statistical analysis was based on a nonparametric Wilcoxon-Mann-Whitney-U test by using a P value at the 0.05 significance level. On day 5, the rabbits were sacrificed and the aorta was referred to histopathology, distribution of iron particles in the vessel wall was analyzed. RESULTS: MRI was feasible in all animals. Three days after injection of ferumoxytol the highest luminal signal intensity measurements were observed in the ferumoxytol group; the highest measurements were five days after injection in the ferumoxtran-10 group (P < 0.05). In the WHHL, susceptibility effects presented as homogeneous dark lines parallel to the aortic wall after ferumoxytol and spotted areas void of signal after ferumoxtran-10. None of these findings were observed in the NZW control groups. CONCLUSION: Ferumoxtran-10 and ferumoxytol at a respective dose of 250 mumol/kg appear well suited for atherosclerotic plaque detection with MRI in experimental atherosclerosis. Ferumoxytol warrants further analysis in humans.     

Ferumoxtran-10, a superparamagnetic iron oxide as a magnetic resonance enhancement agent for imaging lymph nodes: a phase 2 dose study

BACKGROUND AND PURPOSE: Dextran-coated ultrasmall superparamagnetic iron oxide ferumoxtran-10 (Combidex) is used in reticuloendothelial MR imaging. Our purpose was to determine the optimal dose and imaging time for lymph node evaluation. MATERIALS: Twenty-four healthy volunteers underwent neck MR imaging before and 6, 12, 24, and 36 hours after receiving 1.1, 1.7, 2.6, or 3.4 mg Fe/kg ferumoxtran-10. Vital signs, serum and urine levels, and adverse events were monitored. Qualitative nodal architecture, size, and signal-intensity changes were assessed on T1-, T2-, and T2*-weighted (fast field-echo 25 degrees or 80 degrees flip angle [FFE-25 or FFE-80]) images. Region-of-interest intensities were measured quantitatively. RESULTS: Consistently strong enhancement in normal nodes was found with 24- and 36-hour T2- and T2*-weighted imaging after 2.6 and 3.4 mg Fe/kg doses. No serious adverse events occurred. With 2.6 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 100% and 100% (vs 88% and 88%) with T2-weighted, 96% and 96% (vs 73% and 85%) with FFE-25, and 100% and 92% (vs 85% and 88%) with FFE-80 sequences. With 3.4 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 89% and 79% (vs 75% and 75%) with T2-weighted, 84% and 79% (vs 95% and 100%) with FFE-25, and 95% and 79% (vs 95% and 80%) with FFE-80 sequences. CONCLUSION: Ferumoxtran-10 nodal imaging appears to be effective and safe. Signal intensity and specificity for normal nodes were best 24 or 36 hours after 2.6 and 3.4 mg Fe/kg doses. Nodal conspicuity was best with T2- and T2*-weighted sequences.     

Transient osteoporosis of the hip: MR imaging

Three patients with transient osteoporosis of the hip underwent magnetic resonance (MR) imaging. MR images showed decreased signal intensity of bone marrow in the femur on T1-weighted images and increased signal intensity relative to the intensity of normal bone marrow on T2-weighted images. Joint effusions were seen on MR images of all patients on T2-weighted images. The findings on MR images concurred with histologic findings, such as increased bone turnover and mild inflammatory reaction, in one patient. The clinical symptoms and abnormalities on MR images regressed completely within 6-10 months. Familiarity with the distinct features of transient osteoporosis on MR images may be important in the differential diagnosis of adults with hip pain.     

Ferumoxtran-10-enhanced MR imaging of the bone marrow before and after conditioning therapy in patients with non-Hodgkin lymphomas

To quantify permeability changes of the “blood–bone marrow barrier” (BMB) and to detect malignant bone marrow infiltrations before and after conditioning therapy for subsequent leukapheresis using ferumoxtran-10-enhanced magnetic resonance (MR) imaging. Twenty-two patients with malignant non-Hodgkin lymphomas (NHL), including 9 patients (group A) before and 13 patients (group B) after conditioning therapy, underwent MR of the spine before and after infusion of ferumoxtran-10 (0.045 mmol Fe/kg BW). Pulse sequences comprised dynamic T1-GE and pre- and post-contrast T1-SE and STIR sequences. Dynamic ΔSI-data were correlated with the quantity of mobilized CD34+ cells. In addition, the number of focal bone marrow lesions was compared before and after ferumoxtran-10 administration. Dynamic ΔSI-data were higher in group B than in group A, indicating an increased BMB permeability after conditioning therapy. However, ΔSI-data did not correlate with the quantity of mobilized CD34+ cells. Ferumoxtran-10-enhanced STIR images demonstrated a significant signal decline of the normal, non-neoplastic bone marrow and a significantly increased detection of focal neoplastic lesions compared to pre-contrast images (P<0.05). Ferumoxtran-10 depicted the bone marrow response to conditioning therapy by an increase in BMB-permeability, which, however, did not correlate with the number of mobilized CD34+ cells. Ferumoxtran-10 improved the detection of focal bone marrow lesions significantly (P<0.05).     

A pilot investigation of new superparamagnetic iron oxide (ferumoxytol) as a contrast agent for cardiovascular MRI

Purpose: To evaluate the imaging potential of ferumoxytol, a new superparamagnetic iron oxide colloidal blood pool contrast agent.Materials and Methods: Magnetic resonance (MR) imaging at 1.5 Tesla was performed before and after intravenous injection of ferumoxytol using escalating doses of 0.4, 0.8, 1.2 and 1.6 mg Fe/kg for a total of 4 mg Fe/kg in five subjects imaged with 3D MR Angiography (MRA) of the trifurcation after each dose. In five subjects cardiac cine MRI was performed pre and post 4.0 mg Fe/kg. Image quality was assessed by measuring signal to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the vascular structures. Pre- and post-dose urine and blood tests as well as EKG/vital sign monitoring were performed to evaluate safety and blood samples were collected for T1 relaxivity measurements.Results: Cumulative doses of 0, 0.4, 1.2, 2.4 and 4 mg Fe/kg yielded mean SNR in the arteries of 10, 16, 39, 57 and 69 respectively indicating that the higher doses produced higher SNR on 3D vascular images. Similarly aorta SNR on 2D time-of-flight increased from 11.8 without Fe to 15.4 post Fe (p = 0.004) indicating improved image quality on MRA sequences optimized for use without contrast. At 4 mg Fe/kg there was a substantial T1 shortening measured in the blood from 1990 ± 573 ms to 80 ± 42 ms (p < 0.0001), corresponding to the increased SNR. Images of large vascular structures including cardiac chambers, aorta, and pulmonary arteries were excellent post ferumoxytol but images of smaller arteries of the trifurcation were difficult to evaluate due to enhancement of the overlapping veins. No serious adverse events occurred.Conclusion: The new superparamagnetic iron oxide colloid ferumoxytol is a promising blood pool agent especially for cardiac, aorta and pulmonary imaging.     

Osteomyelitis in children: gadolinium-enhanced MR imaging.

Fifteen pediatric patients with biopsy- or culture-proved nonspinal osteomyelitis were studied with magnetic resonance (MR) imaging. Osteomyelitis was acute in seven patients, subacute in three, and chronic in five. Four patients had subperiosteal abscesses, one had a large associated soft-tissue abscess, and one had an intraosseous (Brodie) abscess. Areas of active inflammation had decreased marrow signal intensity on T1-weighted images, increased signal intensity on T2-weighted images, and enhancement on T1-weighted images obtained after gadopentetate dimeglumine administration (n = 10). Abscesses were rim enhancing (n = 3) or not (n = 2) with gadolinium-enhanced MR imaging. Nonenhancing areas presumably represented necrotic material. Gadolinium-enhanced MR imaging assisted in definition of the presence and extent of nonvascularized fluid collections within the bone and/or adjacent soft tissues and the extent of bone involvement in patients with chronic osteomyelitis. It also helped guide surgical debridement of intraosseous disease (n = 7) and open or percutaneous drainage of subperiosteal or soft-tissue fluid collections (n = 5).     

MR imaging of infectious spondylitis

MR images of 14 patients with pyogenic and three patients with tuberculous infectious spondylitis were studied to develop criteria for diagnosis. T1-weighted scans, 800/20 (TR/TE), were obtained in 17 patients and T2-weighted scans, greater than 2000/30,80, were obtained in 14. In seven patients, T2*-weighted scans (gradient-recalled acquisition into steady state, 25/15/5-7 degrees [TR/TE/flip angle]) and short-T1 inversion-recovery scans (STIR), 1400/150/40 (TR/TI/TE), as well as fat and water images (using a suppression technique), were obtained. Unenhanced and gadopentetate-dimeglumine-enhanced scans were obtained in four patients. In all but two patients with pyogenic infectious spondylitis, the T1-weighted sagittal scan showed characteristic findings: narrowed disk space, low signal intensity in the marrow of at least two adjacent vertebrae, subligamentous or epidural soft-tissue masses, and erosion of cortical bone. In one patient the T1-weighted scan was normal and abnormalities could be detected only on the T2-weighted scan. The remaining patient had abnormal marrow signal on the T1-weighted scan but only in one vertebral body. On T2-weighted images the major findings were a narrowed disk space with variable signal changes, abnormal high signal in marrow of at least two adjacent vertebrae, high-signal subligamentous or epidural masses, and cortical bone erosion. The findings in the three patients with tuberculous spondylitis included areas of increased and decreased signal intensity in vertebrae on T1-weighted images. Disk spaces were relatively spared given the extent of disease. Extraosseous soft-tissue components could be large. Bone erosion was best seen on the first echo of a T2-weighted sequence and on a water image; the latter was most reliable since it had no chemical-shift artifact. The use of gadopentetate dimeglumine could obscure or clarify MR findings, depending on the situation. T1- and T2-weighted MR images should be obtained for assessment of infectious spondylitis. STIR scans are particularly helpful. Fat images can be useful in subtle presentations, since they are very sensitive to marrow replacement, and gadopentetate dimeglumine may be helpful for epidural delineation of disease.     

High signal intensity of intervertebral calcified disks on T1-weighted MR images resulting from fat content

Objective To explain a cause of high signal intensity on T1-weighted MR images in calcified intervertebral disks associated with spinal fusion.Design and patients Magnetic resonance and radiological examinations of 13 patients were reviewed, presenting one or several intervertebral disks showing a high signal intensity on T1-weighted MR images, associated both with the presence of calcifications in the disks and with peripheral fusion of the corresponding spinal segments. Fusion was due to ligament ossifications (n=8), ankylosing spondylitis (n=4), or posterior arthrodesis (n=1). Imaging files included X-rays and T1-weighted MR images in all cases, T2-weighted MR images in 12 cases, MR images with fat signal suppression in 7 cases, and a CT scan in 1 case. Histological study of a calcified disk from an anatomical specimen of an ankylosed lumbar spine resulting from ankylosing spondylitis was examined.Results The signal intensity of the disks was similar to that of the bone marrow or of perivertebral fat both on T1-weighted MR images and on all sequences, including those with fat signal suppression. In one of these disks, a strongly negative absorption coefficient was focally measured by CT scan, suggesting a fatty content. The histological examination of the ankylosed calcified disk revealed the presence of well-differentiated bone tissue and fatty marrow within the disk.Conclusion The high signal intensity of some calcified intervertebral disks on T1-weighted MR images can result from the presence of fatty marrow, probably related to a disk ossification process in ankylosed spines.     

Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging

PURPOSE: To prospectively evaluate ferumoxtran-10-enhanced magnetic resonance (MR) imaging for nodal staging in patients with urinary bladder cancer. MATERIALS AND METHODS: Fifty-eight patients with proved bladder cancer were enrolled. Results of MR imaging performed before and after injection of ferumoxtran-10 were compared with histopathologic results in surgically removed lymph nodes. High-spatial-resolution three-dimensional T1-weighted magnetization-prepared rapid acquisition gradient-echo (voxel size, 1.4 x 1.4 x 1.4 mm) and T2*-weighted gradient-echo (voxel size, 0.8 x 0.8 x 3.0 mm) sequences were performed before and 24 hours after injection of ferumoxtran-10 (2.6 mg iron per kilogram of body weight). On precontrast images, lymph nodes were defined as malignant by using size and shape criteria (round node, >8 mm; oval, >10 mm axial diameter). On postcontrast images, nodes were considered benign if there was homogeneous decrease in signal intensity and malignant if decrease was absent or heterogeneous. Qualitative evaluation was performed on a node-to-node basis. Sensitivity, specificity, predictive values, and accuracy were evaluated with logistic regression analysis. RESULTS: In 58 patients, 172 nodes imaged with use of ferumoxtran-10 were matched and correlated with results of node dissection. Of these, 122 were benign and 50 were malignant. With nodal size and shape criteria, accuracy, sensitivity, specificity, and positive and negative predictive values on precontrast images were 92%, 76%, 99%, 97%, and 91%, respectively; corresponding values on postcontrast images were 95%, 96%, 95%, 89%, and 98%. In the depiction of pelvic metastases, sensitivity and negative predictive value improved significantly at postcontrast compared with those at precontrast imaging, from 76% to 96% (P < .001) and from 91% to 98% (P < .01), respectively. At postcontrast imaging, metastases (4-9 mm) were prospectively found in 10 of 12 normal-sized nodes (<10 mm); these metastases were not detected on precontrast images. Postcontrast images also showed lymph nodes that were missed at pelvic node dissection in two patients. CONCLUSION: Ferumoxtran-10-enhanced MR imaging significantly improves nodal staging in patients with bladder cancer by depicting metastases even in normal-sized lymph nodes.     

Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging

Superparamagnetic iron oxide MR imaging contrast agents have been the subjects of extensive research over the past decade. The iron oxide particle size of these contrast agents varies widely, and influences their physicochemical and pharmacokinetic properties, and thus clinical application. Superparamagnetic agents enhance both T1 and T2/T2* relaxation. In most situations it is their significant capacity to reduce the T2/T2* relaxation time to be utilized. The T1 relaxivity can be improved (and the T2/T2* effect can be reduced) using small particles and T1-weighted imaging sequences. Large iron oxide particles are used for bowel contrast [AMI-121 (i.e. Lumirem and Gastromark) and OMP (i.e. Abdoscan), mean diameter no less than 300 nm] and liver/spleen imaging [AMI-25 (i.e. Endorem and Feridex IV, diameter 80-150 nm); SHU 555A (i.e. Resovist, mean diameter 60 nm)]. Smaller iron oxide particles are selected for lymph node imaging [AMI-227 (i.e. Sinerem and Combidex, diameter 20-40 nm)], bone marrow imaging (AMI-227), perfusion imaging [NC100150 (i.e. Clariscan, mean diameter 20 nm)] and MR angiography (NC100150). Even smaller monocrystalline iron oxide nanoparticles are under research for receptor-directed MR imaging and magnetically labeled cell probe MR imaging. Iron oxide particles for bowel contrast are coated with insoluble material, and all iron oxide particles for intravenous injection are biodegradable. Superparamagnetic agents open up an important field for research in MR imaging.     

Diffusion-weighted MR imaging offers no advantage over routine noncontrast MR imaging in the detection of vertebral metastases

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging of the spine has been used to differentiate benign from pathologic vertebral body compression fractures. We sought to determine the utility of diffusion-weighted MR imaging in the detection of vertebral metastases and to compare it with conventional noncontrast T1- and T2-weighted MR imaging. METHODS: Fifteen patients with metastases to the spine were studied using conventional MR imaging and diffusion-weighted imaging. Blinded review of all images was undertaken, and patients were categorized according to whether they had focal or multiple lesions. The signal intensity of the lesions was compared on T1-, T2- (fast spin-echo), and diffusion-weighted images. RESULTS: In five patients with focal disease, metastases were hypointense on T1-weighted images; hypointense (n = 2), isointense (n = 1), or hyperintense (n = 2) on T2-weighted images; and hypointense (n = 3) or hyperintense (n = 2) on diffusion-weighted images with respect to presumed normal bone marrow. In 10 patients with disease in multiple sites, all lesions were hypointense on T1-weighted images; hypointense (n = 2), isointense (n = 4), hyperintense (n = 2), or mixed (n = 2) on T2-weighted images; and hypointense (n = 5), hyperintense (n = 3), or mixed (n = 2) on diffusion-weighted images with respect to presumed normal bone marrow. CONCLUSION: As used in this study, diffusion-weighted MR imaging of the spine showed no advantage in the detection and characterization of vertebral metastases as compared with noncontrast T1-weighted imaging, but was considered superior to T2-weighted imaging.     

Bone bruises: MR characteristics and histological correlation in the young pig

PURPOSE: To correlate magnetic resonance (MR) signal characteristics of bone bruises with histological findings. MATERIALS AND METHODS: In 14 tibiae of young pigs, bone bruises were created in the proximal tibial metaphysis. The signal intensity seen on the MR images were correlated with histological findings. The following findings were evaluated: (a) changes of signal intensity on the tibiae; (b) changes of histology on the tibiae; and (c) changes of (a) and (b) on follow-up examinations. RESULTS: We observed three types of injuries on T1-weighted images: focal or diffuse low signal, normal signal and linear low signal intensities. Severe hemorrhagic areas showed low signal intensities on all sequences of MR imaging. Fast spin-echo (FSE) T2-weighted images showed a more distinct low signal intensity than T1-weighted images. FSE short tau inversion recovery (STIR) and FSE fat saturated (FSE-FS) T2-weighted images showed similar signal intensities with FSE T2-weighted images. FS T1-weighted enhanced images showed low signal intensities with variable enhancements. Upon histological examination, hemorrhages and edemas were prominent at the subcortical areas of the contusion sites. The areas of dense, low signal intensities in all imaging sequences showed signs of severe hemorrhage. The areas of diffuse low signal and enhanced areas showed mixed areas of hemorrhages and edemas. Follow-up MR imaging showed evolution of the processes of hemorrhages and edemas with fatty marrow changes. CONCLUSIONS: MR imaging can depict changes in the bone marrow resulting from direct injury to the bone. MR imaging is a useful tool for evaluating the evolution of bone bruises.     

Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization?

OBJECTIVE: Ferumoxtran-10 is a lymphotropic MR contrast agent that is currently under investigation. It has been shown to be effective in staging lymph nodes of patients with various primary malignancies. The current technique with ferumoxtran-10 involves imaging before and 24 hr after contrast administration. The purpose of this study was to evaluate the accuracy of ferumoxtran-10-enhanced images alone in characterizing lymph nodes for oncologic staging 24 hr after contrast enhancement. MATERIALS AND METHODS: Seventy-seven patients (58 men, 19 women) with proven primary cancer (bladder [n = 20], breast [n = 10], endometrial [n = 1], renal [n = 3], penile [n = 4], prostate [n = 31], rectal [n = 1], testicular [n = 5], and ureteral [n = 2]) who were scheduled for surgical lymph node dissection were enrolled in the study. In these patients, 169 lymph nodes (mean size, 11.2 mm) were evaluated on T2*-weighted gradient-refocused echo MRI at l.5 T both before and 24-36 hr after the IV administration of ferumoxtran-10 (2.6 mg Fe/kg). Two blinded reviewers with differing levels of interpreting experience separately performed qualitative image evaluation. A 6-point scale was used to characterize lymph nodes on contrast-enhanced images alone and on combined unenhanced and contrast-enhanced images. Receiver operating characteristic (ROC) analysis was performed separately for both reviewers. RESULTS: Of the 169 lymph nodes evaluated, 55 were benign and 114 malignant by histopathologic analysis. The results of the ROC analysis comparing contrast-enhanced images ([A(z) = area under ROC curve] reviewer 1, A(z) = 0.92; reviewer 2, A(z) = 0.94) alone with combined unenhanced and contrast-enhanced images (reviewer 1, A(z) = 0.94; reviewer 2, A(z) = 0.93) showed a statistically significant difference (p = 0.01) for reviewer 1 but no difference for reviewer 2 (p = 0.88). Reviewer 2 was more experienced in interpreting ferumoxtran-10-enhanced images than reviewer 1. CONCLUSION: On ferumoxtran-10-enhanced MR lymphangiography, contrast-enhanced images alone may suffice for lymph node characterization. However, a certain level of interpretation experience may be required before contrast-enhanced images can be used alone.     

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.     

MR imaging of skeletal metastases from medulloblastoma

The findings of MR imaging in 3 patients with bone metastases from medulloblastoma are reported. The first patient showed focal lesions of low signal intensity on T1-weighted spin echo images at a time when bone scintigraphy was negative for metastases. This patient later developed extensive osteosclerotic lesions visible on plain films. The bone marrow of the second patient showed diffuse low signal intensity on T1-weighted images. After chemotherapy the signal intensity of the bone marrow increased which correlated with a return of normal hematopoietic tissue. A response to chemotherapy was also found on MR imaging and repeat bone marrow biopsies in a third patient. A consistent finding was a low signal intensity on pre-gadolinium images, but the pattern (focal or diffuse abnormal signal intensity) was different in each patient. To our knowledge, this is the first report on MR imaging findings in bone metastases from medulloblastoma.     

Iron-oxide-enhanced MR imaging of bone marrow in patients with non-Hodgkin's lymphoma: differentiation between tumor infiltration and hypercellular bone marrow

The aim of this study was to differentiate normal, hypercellular, and neoplastic bone marrow based on its MR enhancement after intravenous administration of superparamagnetic iron oxides in patients with cancer of the hematopoietic system. Eighteen patients with cancer of the hematopoietic system underwent MRI of the spine before and after infusion of ferumoxides ( n=9) and ferumoxtran ( n=9) using T1- and T2-weighted turbo spin-echo (TSE) and short tau inversion recovery sequences (STIR). In all patients diffuse or multifocal bone marrow infiltration was suspected, based on iliac crest biopsy and imaging such as conventional radiographs, MRI, and positron emission tomography. In addition, all patients had a therapy-induced normocellular ( n=7) or hypercellular ( n=11) reconversion of the normal non-neoplastic bone marrow. The MRI data were analyzed by measuring pre- and post-contrast signal intensities (SI) of hematopoietic and neoplastic marrow and by calculating the enhancement as deltaSI(%) data and the tumor-to-bone-marrow contrast as contrast-to-noise ratios (CNR). Changes in bone marrow signal intensity after iron oxide administration were more pronounced on STIR images as compared with T1- and T2-weighted TSE images. The STIR images showed a strong signal decline of normal and hypercellular marrow 45-60 min after iron oxide infusion, but no or only a minor signal decline of neoplastic bone marrow lesions; thus, deltaSI% data were significantly higher in normal and hypercellular reconverted marrow compared with neoplastic bone marrow lesions ( p<0.05). Additionally, the contrast between focal or multifocal neoplastic bone marrow infiltration and normal bone marrow, quantified by CNR data, increased significantly on post-contrast STIR images compared with precontrast images ( p<0.05). Superparamagnetic iron oxides are taken up by normal and hypercellular reconverted bone marrow, but not by neoplastic bone marrow lesions, thereby providing significantly different enhancement patterns on T2-weighted MR images; thus, superparamagnetic iron oxides are useful to differentiate normal and neoplastic bone marrow and to increase the bone marrow-to-tumor contrast.