Splenic imaging with ultrasmall superparamagnetic iron oxide ferumoxtran-10 (AMI-7227): preliminary observations

PURPOSE: Ferumoxtran-10 (ultrasmall superparamagnetic iron oxide; Combidex, AMI-7227) is a long-circulating MR contrast agent with reticuloendothelial uptake known to enhance tissue T1 and T2 relaxation rates. The purpose of this study was to assess the effect of ferumoxtran-10-enhanced MRI in evaluating focal splenic lesions. METHOD: Eighteen patients underwent MR evaluation of the spleen. Two of these patients with exophytic normal splenic tissue (splenules) and 13 of these patients with 24 focal splenic lesions (7 cysts, 2 hemangiomas, 7 metastases, 1 infarct, 7 lymphoma) were assessed by T1-weighted gradient echo and T2-weighted fast SE MRI following intravenous administration of ferumoxtran-10 (1.1 mg of Fe/kg). Qualitative analysis involving improved lesion detection and/or characterization, additional information from postcontrast images affecting staging, and patient management was performed. Quantitative measurements of lesion-to-spleen contrast-to-noise ratio were also performed. RESULTS: Additional information was provided by ferumoxtran-10-enhanced images in 15 of 18 patients. In 8 of 15 (53%) patients, improved lesion detection (i.e., number of lesions) was obtained on contrast-enhanced images. Improved lesion visualization (i.e., conspicuity) was noted in 11 of 15 (73%) of patients. In 10 of 15 (67%) patients, postcontrast imaging provided additional information leading to lesion characterization. Staging of disease and patient management were affected in 5 of 15 (33%) and 6 of 15 (40%) patients, respectively. CONCLUSION: Ferumoxtran-10 is a promising contrast agent for the evaluation of focal splenic lesions.     

An exploratory study of ferumoxtran-10 nanoparticles as a blood-brain barrier imaging agent targeting phagocytic cells in CNS inflammatory lesions

BACKGROUND AND PURPOSE: Iron oxide-based contrast agents have been investigated as more specific MR imaging agents for central nervous system (CNS) inflammation. Ferumoxtran-10 is a virus-size nanoparticle, taken up by reactive cells, that allows visualization of the phagocytic components of CNS lesions. Ferumoxtran-10 was compared with standard gadolinium-enhanced MR images in this exploratory trial to assess its potential in evaluation of CNS lesions with inflammatory aspects, including lymphoma, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and vascular lesions. METHODS: Twenty-three patients with different types of intracranial "inflammatory" lesions underwent standard brain MR with and without gadolinium, followed an average of 10 days later by a ferumoxtran-10 scan. Patients were imaged 24 hours after infusion of 2.6 mg/kg ferumoxtran-10. All MR images were evaluated subjectively by 4 investigators for a difference in enhancement patterns, which could be useful in differential diagnoses. RESULTS: In 5 cases, (one ADEM, 2 stroke, one cavernous venous vascular malformation, one primary central nervous lymphoma) the ferumoxtran-10 scan showed higher signal intensity, larger area of enhancement, or new enhancing areas compared with gadolinium. Most MS patients showed less enhancement with ferumoxtran-10 than with gadolinium. CONCLUSION: Ferumoxtran-10 showed different enhancement patterns in a variety of CNS lesions with inflammatory components in comparison to gadolinium. The impact of timing and therapy need further evaluation to better assess ferumoxtran-10 in addition to gadolinium as contrast agents for use in diagnosis and monitoring therapy in patients with CNS inflammatory lesions.     

USPIO-enhanced magnetic resonance imaging for nodal staging in patients with head and neck cancer

PURPOSE: To determine the accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) for nodal staging in patients with head and neck cancer. MATERIALS AND METHODS: Twenty patients with carcinomas of the upper aerodigestive tract were prospectively enrolled. MRI was performed before and 24-36 hours after intravenous infusion of an USPIO agent, ferumoxtran-10 (Sinerem; Guerbet, France; and Combidex; Advanced Magnetics) at a dose of 2.6 mg Fe/kg using T2-weighted spin-echo and gradient-echo sequences. Surgery was performed the same day or the day after the ferumoxtran-10-enhanced MR examination. Based on MRI, selected nodes were surgically removed and directly correlated with pathology using hematoxylin-eosin (H&E) and Perls stainings. RESULTS: A total of 63 nodes were studied; 36 were nonmetastatic, 25 metastatic, and two inflammatory. Ferumoxtran-10-enhanced MRI allowed diagnosis of 24 metastatic and 30 nonmetastatic nodes, yielding a sensitivity of 96%, a specificity of 78.9%, a positive predictive value of 75%, and a negative predictive value of 96.8%, compared to 64%, 78.9%, 66.6%, and 76.9%, respectively, for nonenhanced MRI. Accuracy of ferumoxtran-10-enhanced MRI was 85.7%. The gradient-echo T2-weighted sequence was the most accurate to detect signal loss in nonmetastatic nodes. CONCLUSION: USPIO-enhanced MRI is useful for nodal staging of patients with head and neck cancers.     

Ultrasmall superparamagnetic iron-oxide-enhanced MR imaging of normal bone marrow in rodents: original research original research

RATIONALE AND OBJECTIVES: The objective is to compare three different ultrasmall superparamagnetic iron oxides (USPIOs) for magnetic resonance (MR) imaging of normal bone marrow in rodents. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data

The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide contrast agent, are presented. One hundred and four patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg. Overall, 15% patients reported a total of 33 adverse events, regardless of causality. The adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and rash (2.9%). No serious adverse events were reported during the 48 hour observation period. There were no clinically significant effects on vital signs, physical examination, and laboratory results. Ferumoxtran-10 is a safe and well tolerated MR contrast agent.     

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.     

Bone involvement in patients with lymphoma: the role of FDG-PET/CT

Purpose To evaluate the diagnostic impact and clinical significance of FDG-avid bone lesions detected by FDG-PET/CT in patients with lymphoma. Methods The study population comprised 50 consecutive patients (mean age 41.7±15.5 years; 27 female, 23 male; 41 staging, 9 restaging) with Hodgkin’s disease (n=22) or aggressive non-Hodgkin’s lymphoma (n=28) in whom FDG-avid bone lesions were detected by FDG-PET/CT. All patients had either direct biopsy of the FDG-avid bone lesion (n=18), standard bone marrow biopsy at the iliac crest (BMB; n=43) or both procedures (n=11). In 15 patients, additional MRI of the bone lesions was performed. All patients underwent FDG-PET/CT after the end of treatment. All CT images of FDG-PET/CT scans were analysed independently regarding morphological osseous changes and compared with FDG-PET results. Results In the 50 patients, 193 FDG-avid lesions were found by PET/CT. The mean standardised uptake value was 6.26 (±3.22). All direct bone biopsies (n=18) of the FDG-avid lesions proved the presence of lymphomatous infiltration. BMB (n=43) was positive in 12 patients (27.9%). In CT, 32 of 193 (16.6%) lesions were detected without the PET information. No additional morphological bone infiltration was detected on CT compared with FDG-PET. All morphological bone alterations on CT scans persisted after the end of therapy. Additional PET/CT information regarding uni- or multifocal bone involvement resulted in lymphoma upstaging in 21 (42%) patients compared with the combined information provided by CT and BMB. Conclusion In patients with FDG-avid bone lesions, FDG-PET is superior to CT alone or in combination with unilateral BMB in detecting bone marrow involvement, leading to upstaging in a relevant proportion of patients.     

Prospective study of bone marrow infiltration in aggressive lymphoma by three independent methods: whole-body MRI, PET/CT and bone marrow biopsy

PURPOSE: Initial lymphoma staging requires bone marrow assessment in aggressive lymphomas. Bone marrow lymphoma infiltration is routinely assessed by bone marrow biopsy (BMB), considered as the "gold standard". The aim of this study was to compare the performance of BMB, whole-body MRI and PET/CT for evaluation of BM infiltration. METHODS: Patients with newly diagnosed aggressive lymphoma were evaluated by BMB, MRI and PET/CT. Two radiologists, two nuclear medicine physicians and one pathologist independently assessed the results of the three modalities. Bone was considered as involved if BM was positive or if PET/CT or MRI was positive and if there was a resolution of the abnormal image shown on PET/CT or MRI halfway or at the end of therapy. RESULTS: Both MRI and PET/CT detected bone marrow lesions in the 9/43 patients, but two patients with multiple lesions had more lesions detected by PET/CT compared to MRI. Among these nine patients, two with an iliac crest lesion detected by both MRI and PET/CT had bone marrow involvement with large-cell lymphoma on histological examination. The other seven patients had focal MRI and PET/CT lesions in areas other than the iliac crest, where the blind BMB was done. The other patients had bone marrow without large-cell lymphoma involvement. In all cases, after lymphoma therapy bone marrow involvement regressed on histological examination, PET and MRI. CONCLUSION: These preliminary results suggest that non-invasive morphological procedures could be superior to BMB for bone marrow assessment in aggressive lymphomas. Ongoing study is underway to validate these results.     

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.     

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.     

Monitoring radiation-induced changes in bone marrow histopathology with ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI.

The purpose of this study was to monitor radiation-induced alterations of the blood-bone marrow barrier (BMB) and the reticuloendothelial system (RES) with AMI-227-enhanced magnetic resonance imaging (MRI). Twenty New Zealand white rabbits (n = 10 following total body irradiation and n = 10 controls) underwent AMI-227-enhanced MRI. Pulse sequences included dynamic fast low-angle shot (FLASH; TR/TE 50/4 msec, flip angle 60 degrees) MRI and static T1- and T2-weighted spin-echo (SE) and turbo-SE sequences of the lumbar spine and sacrum. Bone marrow enhancement was quantified as delta signal intensity (SI) (%) =|[(SIpost - SIpre)/SIpre] x 100%| and compared with histopathology, including iron stains and electron microscopy. Dynamic bone marrow deltaSI (%) data steadily increased up to 10-15 minutes after AMI-227 administration, while blood deltaSI (%) data stayed nearly constant, histologically corresponding to iron oxide leakage into the bone marrow interstitium. This bone marrow contrast enhancement increased significantly following irradiation, corresponding to alterations of the endothelial lining of the bone marrow sinusoids. Late postcontrast images exhibited a significant positive T1 enhancement and negative T2 enhancement of the normal bone marrow, which further increased with irradiation due to increased RES activity. Irradiation-induced changes in bone marrow physiology could be reliably assessed with AMI-227-enhanced MRI.     

Early and late bone-marrow changes after irradiation: MR evaluation

Knowledge of the chronologic evolution of bone-marrow changes during and after radiation therapy is essential in differentiating normal postradiation changes from other marrow abnormalities. The appearance of the lumbar vertebral bone marrow was studied on 55 serial spin-echo and short-T1 inversion-recovery (STIR) MR images obtained in 14 patients receiving radiation therapy for Hodgkin disease, seminoma, or prostate carcinoma. Images were obtained before, at weekly intervals during, and at various monthly intervals up to 14 months after a 3- to 6-week course of fractionated paravertebral lymph-node irradiation of 1500-5000 rad (15-50 Gy). During the first 2 weeks of therapy, there was no definite change in the appearance of the marrow on spin-echo images; however, there was an increase in signal intensity on the STIR images, apparently reflecting early marrow edema and necrosis. Between weeks 3 and 6, the marrow showed an increasingly heterogenous signal and prominence of the signal from central marrow fat, shown best on T1-weighted images. Late marrow patterns (6 weeks to 14 months after therapy) varied and consisted of either homogenous fatty replacement or a band pattern of peripheral intermediate signal intensity, possibly representing hematopoietic marrow surrounding the central marrow fat. No focal marrow lesions or soft-tissue edema were identified during the course of radiation therapy; their presence should raise the possibility of the presence of a pathologic process other than radiation change. These data suggest that MR can detect radiation-induced marrow changes as early as 2 weeks after starting therapy, and that there are at least two distinct types of late marrow MR patterns.     

Preclinical safety and pharmacokinetic profile of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide magnetic resonance contrast agent

OBJECTIVES: This report presents an overview of preclinical data available on ferumoxtran-10, an ultrasmall superparamagnetic iron oxide nanoparticular contrast agent proposed for lymph node magnetic resonance imaging. MATERIALS AND METHODS: Pharmacokinetic, safety pharmacology, single- and repeat-dose toxicity, reproduction toxicity, and genotoxicity studies were performed with ferumoxtran-10 given intravenously (bolus injection) in mice, rats, rabbits, dogs, and monkeys. RESULTS: Ferumoxtran-10 was taken up by macrophages, mostly in liver, spleen, and lymph nodes, within 24 hours after bolus injection and underwent progressive metabolism. Toxicity was observed only at very high exposure levels and mainly was linked to a massive iron load after repeated injections. Ferumoxtran-10 was not mutagenic but was teratogenic in rats and rabbits. DISCUSSION: The preclinical pharmacokinetic and safety profile of ferumoxtran-10 appears to be satisfactory in view of its proposed use as a single-dose diagnostic agent in human for MR imaging of lymph nodes.     

Intramedullary chondroid tumors of bone: correlation of abnormal peritumoral marrow and soft-tissue MRI signal with tumor type

 Objective. To determine whether enchondromas and chondrosarcomas can be differentiated on the basis of peritumoral MR signal abnormality. Design. STIR and T2-weighted MRI images were retrospectively assessed for the presence and extent of abnormal peritumoral marrow and soft-tissue signal. The cause of the peritumoral signal abnormality was determined by histologic correlation with resection specimens. The presence or absence of bone destruction was noted. Patients. Twenty-three patients were studied: ten with enchondromas (three men, seven women; ages 33–73 years) and 13 with chondrosarcomas (seven men, six women; ages 25–88 years). Results. Abnormal peritumoral marrow signal was present on STIR images around none of 10 enchondromas and all of 13 chondrosarcomas (P<0.0001). The marrow signal abnormality corresponded histologically to fine marrow fibrosis in all cases. Adjacent abnormal soft-tissue signal was present on STIR images around none of ten enchondromas and eight (62%) of 13 chondrosarcomas (P=0.0026). Abnormal soft-tissue signal was more common around high-grade than low-grade chondrosarcomas (100% vs 38%, P=0.028), and was more extensive (mean extent 28 mm vs 8 mm; P>0.04). In the subset of tumors without bone destruction, peritumoral marrow signal abnormality was present around none of ten enchondromas and all of five chondrosarcomas (P=0.0003); abnormal soft-tissue signal was present around none of ten enchondromas and two of five chondrosarcomas (P>0.05). Conclusion. Abnormal marrow or soft-tissue signal around a chondroid tumor is suggestive of chondrosarcoma, even in the absence of bone destruction. STIR images are necessary for adequate detection of peritumoral signal abnormalities.     

Initial experience with FSE STIR whole-body MR imaging for staging lymphoma in children

Our objective was to compare fast spin-echo (FSE) short inversion time inversion recovery (STIR) whole-body MR imaging with standard procedures in staging children with lymphoma. Eight children (age range, 2–16 years) underwent multi-station FSE STIR whole-body MR at initial staging (n=5) or for restaging following completion of therapy (n=5). Whole-body MR and conventional staging procedures, including CT (n=10), gallium-67 scintigraphy (n=9), bone scintigraphy (n=3) and bone marrow biopsy (n=7) were retrospectively compared for detection of sites involved by lymphoma and for the assigned stage. FSE STIR whole-body MR detected more sites of possible lymphomatous involvement at initial staging (87/88) and at restaging (5/5) than did conventional imaging (74/88, 3/5). MR was more sensitive than conventional imaging in detecting bone marrow involvement at initial staging. Following treatment, however, residual and therapy-induced bone marrow signal abnormalities could not be differentiated from lymphomatous involvement. Detection of nodal and visceral involvement correlated well. Our results suggest that FSE STIR whole-body MR imaging is a sensitive technique for evaluating lymphomatous involvement of bone marrow as well as non-marrow sites. Larger prospective trials are needed to determine if FSE STIR whole-body MR can replace standard radiographic procedures for initial staging and contribute in the follow-up of lymphoma in children.     

Bone marrow changes on STIR MR images of asymptomatic feet and ankles

The purpose of this study was to evaluate the prevalence, pattern and size of bone marrow changes on short-tau inversion recovery (STIR) magnetic resonance (MR) images of asymptomatic feet and ankles. In 78 asymptomatic volunteers (41 women, 37 men; median age 47 years; range 23–83 years) sagittal STIR MR images of hindfoot and midfoot were reviewed for various patterns of high signal changes in bone marrow. The size of these bone marrow changes was measured, and signal intensity was rated semi-quantitatively using a scale from 0 (=normal) to 10 (=fluid-like). Fifty percent (39/78) of all volunteers had at least one bone marrow change. Thirty-six percent (28/78) of all volunteers had edema-like changes, 26% (20/78) had necrosis-like changes, and 5% (4/78) had cyst-like changes. The long diameters of all changes varied between 4 mm and 16 mm (median 7.5 mm). The median signal intensity for all changes was 5.0 (range 1–10). Bone marrow changes on STIR MR images are commonly detected in asymptomatic feet and ankles. However, such changes tend to be small (<1 cm) or subtle.     

Comparison of a conventional cardiac-triggered dual spin-echo and a fast STIR sequence in detection of spinal cord lesions in multiple sclerosis

The current optimal imaging protocol in spinal cord MR imaging in patients with multiple sclerosis includes a long TR conventional spin-echo (CSE) sequence, requiring long acquisition times. Using short tau inversion recovery fast spin-echo (fast STIR) sequences both acquisition time can be shortened and sensitivity in the detection of multiple sclerosis (MS) abnormalities can be increased. This study compares both sequences for the potential to detect both focal and diffuse spinal abnormalities. Spinal cords of 5 volunteers and 20 MS patients were studied at 1.0 T. Magnetic resonance imaging included cardiac-gated sagittal dual-echo CSE and a cardiac-gated fast STIR sequence. Images were scored regarding number, size, and location of focal lesions, diffuse abnormalities and presence/hindrance of artifacts by two experienced radiologists. Examinations were scored as being definitely normal, indeterminate, or definitely abnormal. Interobserver agreement regarding focal lesions was higher for CSE (ϰ = 0.67) than for fast STIR (ϰ = 0.57) but did not differ significantly. Of all focal lesions scored in consensus, 47 % were scored on both sequences, 31 % were only detected by fast STIR, and 22 % only by dual-echo CSE (n. s.). Interobserver agreement for diffuse abnormalities was lower with fast STIR (ϰ = 0.48) than dual-echo CSE (ϰ = 0.65; n. s.). After consensus, fast STIR showed in 10 patients diffuse abnormalities and dual-echo CSE in 3. After consensus, in 19 of 20 patients dual-echo CSE scans were considered as definitely abnormal compared with 17 for fast STIR. The fast STIR sequence is a useful adjunct to dual-echo CSE in detecting focal abnormalities and is helpful in detecting diffuse MS abnormalities in the spinal cord. Due to the frequent occurrence of artifacts and the lower observer concordance, fast STIR cannot be used alone. Received: 9 September 1999; Revised: 14 December 1999; Accepted: 16 December 1999     

Magnetic resonance imaging of disseminated bone marrow disease in patients treated for malignancy

Magnetic resonance imaging (MRI) is a sensitive method for the diagnosis of bone marrow abnormalities, but its usefulness in detecting active disseminated cancer in this tissue in treated patients has not been determined. We therefore examined 14 children who had been treated for disseminated bone marrow involvement by neuroblastoma (n=6), lymphoma (n=3), Ewing's sarcoma (n=3), osteosarcoma (n=1), and leukemia (n= 1). MRI studies were performed at 21 marrow sites to evaluate residual or recurrent tumor and were correlated with histologic material from the same site. T₁- and T₂-weighted sequences were employed in 21 and 14 studies, respectively; short tau inversion recovery (STIR) in 18; and static gadolinium diethylene triamine pentaacetic acid (Gd-DPTA)-enhanced, T₁-weighted sequences in 13. All MRI studies showed an altered bone marrow signal. Technetium 99m methylene diphosphonate (^99mTc-MDP) bone scintigraphy was also performed (19 studies). On histologic examination, 7 marrow specimens contained tumor, and 14 did not. Of the 7 tumor-positive lesions, all T₁-weighted, 4 of 6 T₂-weighted, and all 6 STIR sequences showed abnormal signal; all 5 GdDTPA-enhanced, T₁-weighted sequences showed enhancement of the lesion. However, abnormal signals were also observed on all T₁-weighted, 6 of 8 T₂-weighted, 11 of 12 STIR, and 5 of 8 Gd-DTPA-enhanced, T₁-weighted images of the tumor-negative sites. In this clinical setting, MRI did not consistently differentiate changes associated with treatment from malignant disease.     

Single-dose contrast agent for intraoperative MR imaging of intrinsic brain tumors by using ferumoxtran-10

BACKGROUND AND PURPOSE: Intraoperative MR imaging (IMRI) has advantages over conventional framed and frameless techniques. IMRI, however, also has some drawbacks, especially related to interpretation of gadolinium-enhanced intraoperative imaging resulting from surgically induced blood brain barrier injury, vascular changes, and hemorrhage. Ultra-small superparamagnetic iron particles like ferumoxtran-10 have a long plasma half-life and are trapped by reactive cells within the tumor. These trapped particles provide a method to demonstrate enhancing lesions without the artifact of repeat gadolinium administration in the face of blood brain barrier and vascular injury. METHODS: We present a review of the literature and the cases of two patients who underwent surgery in which IMRI with ferumoxtran-10 was used. RESULTS: Ultra-small superparamagnetic iron particles represent a method to demonstrate enhancing intrinsic brain tumors without the drawbacks of intraoperative gadolinium enhancement. These lesions appear even on low-field strength IMRI. Ferumoxtran-10, administered preoperatively, provides a stable imaging marker, even after surgical manipulation of the brain. CONCLUSION: Fermumoxtran-10 provides a way to lessen artifactual enhancement during IMRI related to the administration of gadolinium.     

全身MRI与PET/CT在淋巴瘤骨髓浸润诊断及预后中的作用

淋巴瘤是一种血液系统恶性肿瘤。淋巴瘤骨髓浸润(BMI)使疾病分期上升至IV期, 是疾病进展、预后较差的标志。常规部位的骨髓活检(BMB)具有创伤性, 且检出率低。PET/CT与全身MRI的出现, 丰富了BMI的检测手段。PET/CT与全身MRI对于淋巴瘤, 尤其是侵袭性淋巴瘤BMI均具有较高的检出率, 二者孰高孰低, 尚未定论。对于红骨髓、良性骨髓病变(炎症等)、淋巴瘤BMI病灶以及肿瘤治疗后骨髓的变化与骨髓残留或复发病灶, 全身MRI很难区分, 而PET/CT却可以很好地鉴别这些病灶。但是, PET/CT存在电离辐射; 对于惰性淋巴瘤的BMI, 超出PET/CT分辨率的病灶, 可能出现假阴性; 某些情况会限制PET/CT的使用, 包括18F-FDG生理性摄取量可能发生改变的正常组织、18F-FDG摄取相关性炎症、高血糖或高胰岛素血症导致的18F-FDG分布的改变、肿瘤患者治疗后出现的骨髓活化等。然而, 这些情况可以使用全身MRI。因此, 全身MRI和PET/CT相辅相成, 优势互补, 但二者均不能代替BMB。对于常规BMB阴性, 但影像学提示阳性的患者, 在影像学引导下进行BMB, 可以提高BMI的检出率。另外, 全身MRI阳性的淋巴瘤BMI患者与全身MRI阴性的淋巴瘤BMI患者相比, 前者预后可能较差。