A comparison of the sensitivity of MRI after double- and triple-dose Gd-DTPA for detecting enhancing lesions in multiple sclerosis

We compared the number and volume of enhancing lesions detected in patients with multiple sclerosis (MS) seen on post-contrast T(1)-weighted scans obtained after the injection of different gadolinium-DTPA (Gd) doses. Enhanced magnetic resonance imaging (MRI) scans were obtained from 16 patients with relapsing remitting or secondary progressive MS on two different occasions separated by an interval of approximately 24 h. On the first occasion, enhanced scans were obtained 15 min after the injection of a double dose of Gd (0.2 mmol/Kg), on the second 15 min after the injection of a triple dose (0.3 mmol/Kg) of Gd. Scans were assessed by consensus in a random order by two observers unaware of the dose of Gd used. We counted the same 30 enhancing lesions on both double dose and triple dose scans from 9 patients. The mean (SD) volumes of enhancing lesions were 1.7 (2.7) mL on double dose and 1.9 (3.4) mL on triple-dose scans. This difference was not statistically significant. This study demonstrated that double dose of Gd has a sensitivity for detecting MS activity similar to that of a triple dose, with the advantage of a significant cost saving.     

Correlation between enhancing lesion number and volume on standard and triple dose gadolinium-enhanced brain MRI scans from patients with multiple sclerosis.

We investigated the correlations between numbers and volumes of multiple sclerosis (MS) lesions enhancing on standard dose (SD) and triple dose (TD) gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI) scans, to clarify whether the measurement of enhancing lesion volumes or the use of TD MRI give additional information which can not be obtained by counting enhancing lesions on SD scans. SD and TD Gd-enhanced brain MRI scans were obtained every month for three months from 40 MS patients. The numbers of total and new enhancing lesions were counted, and the total volumes of enhancing lesions were measured from each of the four scans obtained with the two techniques. Univariate correlations between enhancing lesion numbers and volumes were assessed. The numbers of total and new enhancing lesions seen either on SD or TD scans were significantly correlated (r = 0.91 and 0.93, respectively). The numbers and volumes of total enhancing lesions were significantly correlated on both SD (r = 0.90), and TD (r = 0.89) scans. Moderate correlations were found between the total number of enhancing lesions on SD scans and the average difference between TD and SD scans for total enhancing lesion number (r = 0.66), and between the number of new enhancing lesions on SD scans and the average difference between TD and SD scans for new enhancing lesion number (r = 0.50). Our findings indicate that, both on SD and TD MRI, the counts and the volumes of total and new enhancing lesions are highly correlated, and that lesion counting may suffice to monitor MS activity. On the contrary, this study confirms the usefulness of TD MRI for a more complete assessment of the acute changes occurring in MS patients.     

Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging.

We performed serial monthly magnetization transfer (MT) imaging to evaluate the prevalence and evolution of structural changes in individual enhancing lesions from patients with multiple sclerosis (MS). Every 4 weeks for 3 months, we obtained dual echo, magnetization transfer (MT) imaging and, 5 min after SD (0.1 mmol/kg) gadolinium-DTPA injection, T1-weighted scans from 10 patients with early relapsing-remitting MS. We measured the MT ratio (MTR) of enhancing lesions seen on the entry scans on co-registered quantitative MTR images at entry and during the follow up. Fourty-two enhancing lesions were identified on the entry scans. According to the "maximal random fluctuation" detected for the normal-appearing white matter MTR values, 16 (38%) lesions were classified as "increasing MTR" lesions, 21 (50%) as "stable MTR" lesions, and 5 (12%) as "decreasing MTR" lesions. The classification of the lesions after the first month of follow up strongly predicted the classification at the end of the follow up (chi squared = 20.35, p = 0.0004). These results indicate that the enhancing lesion population in MS is heterogeneous, and that reparative mechanisms occurring after blood-brain barrier opening are not efficient in only a minority of the enhancing lesions from patients with early relapsing-remitting MS.     

Spinal MR imaging in suspected metastases: correlation with skeletal scintigraphy

Bone scintigraphy (RN) and magnetic resonance imaging (MR) were prospectively and retrospectively correlated in 64 patients with suspected spinal metastatic disease and possible spinal cord compression. Images were retrospectively interpreted and compared with the prospective official RN and MR reports to help decide relative prospective lesion conspicuity. Spinal lesions were confirmed by radiography, computed tomography, myelography or MR and RN follow-up in 56 patients (88%). Prospectively, MR detected 11 lesions not reported on RN while RN detected two lesions not reported on MR. Retrospective review of RN detected six lesions previously not reported. Retrospectively MR showed all lesions. Those lesions seen only in retrospect by RN were rather subtle and would be difficult to detect prospectively. In general, lesions not well seen on RN had relatively more bone marrow abnormality and less cortical bone involvement. In some cases, MR imaging shows spinal marrow lesions not well seen on planar RN.     

Visualization of mouse spinal cord intramedullary arteries using phase‐ and attenuation‐contrast tomographic imaging

Many spinal cord circulatory disorders present the substantial involvement of small vessel lesions. The central sulcus arteries supply nutrition to a large part of the spinal cord, and, if not detected early, lesions in the spinal cord will cause irreversible damage to the function of this organ. Thus, early detection of these small vessel lesions could potentially facilitate the effective diagnosis and treatment of these diseases. However, the detection of such small vessels is beyond the capability of current imaging techniques. In this study, an imaging method is proposed and the potential of phase‐contrast imaging (PCI)‐ and attenuation‐contrast imaging (ACI)‐based synchrotron radiation for high‐resolution tomography of intramedullary arteries in mouse spinal cord is validated. The three‐dimensional vessel morphology, particularly that of the central sulcus arteries (CSA), detected with these two imaging models was quantitatively analyzed and compared. It was determined that both PCI‐ and ACI‐based synchrotron radiation can be used to visualize the physiological arrangement of the entire intramedullary artery network in the mouse spinal cord in both two dimensions and three dimensions at a high‐resolution scale. Additionally, the two‐dimensional and three‐dimensional vessel morphometric parameter measurements obtained with PCI are similar to the ACI data. Furthermore, PCI allows efficient and direct discrimination of the same branch level of the CSA without contrast agent injection and is expected to provide reliable biological information regarding the intramedullary artery. Compared with ACI, PCI might be a novel imaging method that offers a powerful imaging platform for evaluating pathological changes in small vessels and may also allow better clarification of their role in neurovascular disorders.     

Applying functional MRI to the spinal cord and brainstem

Functional magnetic resonance imaging of the spinal cord (spinal fMRI) has facilitated the noninvasive visualization of neural activity in the spinal cord (SC) and brainstem of both animals and humans. This technique has yet to gain the widespread usage of brain fMRI, due in part to the intrinsic technical challenges spinal fMRI presents and to the narrower scope of applications it fulfills. Nonetheless, methodological progress has been considerable and rapid. To date, spinal fMRI studies have investigated SC function during sensory or motor task paradigms in spinal cord injury (SCI), multiple sclerosis (MS) and neuropathic pain (NP) patient populations, all of which have yielded consistent and sensitive results. The most recent study in our laboratory has successfully used spinal fMRI to examine cervical SC activity in a SCI patient with a metallic fixation device spanning the C₄ to C₆ vertebrae, a critical step in realizing the clinical utility of the technique. The literature reviewed in this article suggests that spinal fMRI is poised for usage in a wide range of patient populations, as multiple groups have observed intriguing, yet consistent, results using standard, readily available MR systems and hardware. The next step is the implementation of this technique in the clinic to supplement standard qualitative behavioral assessments of SCI. Spinal fMRI may offer insight into the subtleties of function in the injured and diseased SC, and support the development of new methods for treatment and monitoring.     

Improved sensitivity of MRI in multiple sclerosis by use of extensive standardized procedures

The relative value of two different MRI procedures for the assessment of infratentorial extension in multiple sclerosis (MS) was studied. Multislice spin-echo techniques were used overall. Procedure A consisted of parasagittal T1-weighted images (500/30) and axial T2-weighted images (2500/30, 2500/120). Procedure B consisted of parasagittal T2-weighted images (1600/35, 1600/90). In the parasagittal T2-weighted images clear visualization of MS lesions is achieved because signal intensities of CSF and normal nervous tissue are nearly identical. All images were performed with a 0.5 Tesla MR system. Data were obtained in 98 patients with definite (N = 30) or probable MS (N = 68). Areas with abnormal signal intensity in the infratentorial regions (brainstem, cerebellum, and/or cervical spinal cord) were identified in 44% of the patients with procedure A and in 64% with procedure B. The standard application of the combination of both procedures improves the sensitivity of the MR examination for the diagnosis of MS, the delineation of infratentorial lesions and the correlation between clinical and MR data without excessively increasing imaging time.     

Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging.

The apparent diffusion coefficient (ADC) of tissue provides an indication of the size, shape, and orientation of the water spaces in tissue. Thus, pathologic differences between lesions in multiple sclerosis (MS) patients with different clinical courses may be reflected by changes in ADC measurements in lesions and white matter. Twelve healthy subjects and 35 MS patients with a relapsing-remitting (n = 10), benign (n = 8), secondary progressive (n = 8) and primary progressive (n = 9) clinical course were studied. T2-weighted and post-gadolinium T1-weighted images were obtained using a 1.5 T Signa Echospeed magnetic resonance imaging (MRI) system. Diffusion-weighted imaging was implemented using a pulsed gradient spin echo (PGSE) sequence with diffusion gradients applied in turn along three orthogonal directions in order to obtain the average apparent diffusion coefficient (ADCav). Navigator echo correction and cardiac gating were used to reduce motion artifact. ADC maps were derived using a two point calculation based on the Stejskal-Tanner formula. Diffusion anisotropy was estimated using the van Gelderen formula to calculate an anisotropy index. MS lesions had a higher ADC and reduced anisotropy compared with normal appearing white matter. Highest ADC values were found in gadolinium enhancing lesions and non-enhancing hypointense lesions on T1-weighted imaging. MS white matter had a slightly higher ADC and lower anisotropy than white matter of healthy subjects. Lesion and white matter ADC values did not differ between patients with different clinical courses of MS. There was no correlation between lesion ADC and disability. Diffusion-weighted imaging with measurement of ADC using the PGSE method provides quantitative information on acute edematous MS lesions and chronic lesions associated with demyelination and axonal loss but does not distinguish between clinical subtypes of MS.     

Reduced field-of-view DTI segmentation of cervical spine tissue

The number of diffusion tensor imaging (DTI) studies regarding the human spine has considerably increased and it is challenging because of the spine’s small size and artifacts associated with the most commonly used clinical imaging method. A novel segmentation method based on the reduced field-of-view (rFOV) DTI dataset is presented in cervical spinal canal cerebrospinal fluid, spinal cord grey matter and white matter classification in both healthy volunteers and patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). Due to each channel based on high resolution rFOV DTI images providing complementary information on spinal tissue segmentation, we want to choose a different contribution map from multiple channel images. Via principal component analysis (PCA) and a hybrid diffusion filter with a continuous switch applied on fourteen channel features, eigen maps can be obtained and used for tissue segmentation based on the Bayesian discrimination method. Relative to segmentation by a pair of expert readers, all of the automated segmentation results in the experiment fall in the good segmentation area and performed well, giving an average segmentation accuracy of about 0.852 for cervical spinal cord grey matter in terms of volume overlap. Furthermore, this has important applications in defining more accurate human spinal cord tissue maps when fusing structural data with diffusion data. rFOV DTI and the proposed automatic segmentation outperform traditional manual segmentation methods in classifying MR cervical spinal images and might be potentially helpful for detecting cervical spine diseases in NMO and MS.     

Cervical spine MR imaging using multislice gradient echo imaging: comparison with cardiac gated spin echo

Forty-one patients with suspected cervical spine disorders were studied using multislice gradient echo imaging (GE) technique, with a 1.5-T system. The images were compared to cardiac-gated spin echo (CGSE) images in the diagnosis of suspected cord and spinal disorders. Images were graded for ability to detect cord lesion, cord-CSF contrast, CSF-bone contrast and contrast between CSF and extradural abnormality. The signal-to-noise ratio and contrast-to-noise ratio were used to compare images. There was 44% decrease in contrast between cord lesion and normal cord on GE when compared to CGSE, except for spinal cord hemorrhage. There was a 40% improvement between bone and CSF contrast on GE compared to CGSE. GE images were significantly better qualitatively as well as quantitatively in the detection of extradural lesions. This effect was more marked in axial plane where CGSE images are extremely suboptimal. CGSE images are better than GE for spinal cord lesions, while GE are superior in the diagnosis of degenerative disease in the cervical spine.     

Optimal detection of blood-brain barrier defects with Gd-DTPA MRI—The influences of delayed imaging and optimised repetition time

A computer simulation of Gd-DTPA enhancement in blood-brain barrier defects was used to find the tissue concentration as a function of time after bolus injection for a variety of lesion permeability and leakage space values. High permeability lesions start to decay less than 10 min after injection; while low permeability lesions may not reach their maximum concentration until at least 2 h after injection. The minimum detectable permeability was calculated for a range of leakage space values. For a leakage space of 0.1, 2 h after a standard 0.1 mmol/kg injection a permeability surface area product as low as 0.0005 min⁻¹ still gives detectable enhancement, while 6 min after injection the permeability must be at least six times higher to give detectable enhancement. The simulation shows that the effect of triple dose compared to standard dose cannot be found using cumulative dose experiments where the triple dose is fractionated over a period of 10–30 min.     

Discussion on the usefulness of dose dynamic multi-leaf collimator-based plan to overcome dose limit of spinal cord in high-dose radiotherapy

In this study, the conventional plan was compared with the plan that was based on a dose dynamic multi-leaf collimator (MLC), and a dose dynamic MLC was used to evaluate its usefulness. Then, this study examined if it was possible to perform a high-dose radiation therapy by adjusting the dose limit of the spinal cord when the dose dynamic MLC-based plan was used. First of all, linear accelerator was used to compare the conventional plan with the dose dynamic MLC-based plan. Then, the study was conducted in two methods in order to examine the proper range of the shield for the spinal cord when the dose dynamic MLC was used to adjust the dose of the spinal cord. In the first method, X-omat film was used to perform film dosimetry. In the second method, radiation treatment planning (RTP) system was used to find out the proper range among 0, 3, 6, and 9 mm. When film scan was performed in the each range, respectively, from the spinal cord and under the same conditions, it was confirmed to be appropriate to use the range of 3 mm. When the RTP system was used to perform planning in the shield range of each range, respectively, from the spinal cord, dose-volume histogram (DVH) was a slight difference could be found in the region from 25% to 35%. On the contrary, no radiation exposure was found in the region of 35% or higher for all of the each range. Consequently, if MLC is selected in consideration of the planning target volume (PTV), the most proper value can be obtained by selecting the range of 3 mm. Next, the DVH was compared to examine the relationship in PTV when the each range was used for planning. All of the ranges showed the same pattern up to the point of 90%. However, the results were different in the region of higher than 90% because the dose was low for the spinal cord, and a relatively useful dose was used for PTV when the range was 3 mm.     

NMR studies in the relapsing experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in the strain 13 guinea pig

Juvenile strain 13 guinea pigs sensitized with an emulsion of whole isologous central nervous system (CNS) tissue in complete Freund's adjuvant in the first two weeks of life develop a relapsing-remitting form of experimental allergic encephalomyelitis (EAE) which resembles multiple sclerosis (MS) both clinically and pathologically. In order to determine if this experimental model could be used to identify the tissue factors which contribute to the magnetic resonance imaging (MRI)-detected lesions in MS, we measured T1 and T2 relaxation times, tissue specific gravity and histology throughout the entire CNS in vitro in eighteen animals during the acute phase (first attack), and twenty-one animals during further periods of clinical worsening (relapses) and recovery (remissions). The neuropathological findings of spinal cord meningeal inflammation, perivascular and parenchymal infiltration (myelitis and encephalitis) and demyelination were more marked during periods of clinical worsening than when the animal had recovered clinically. Even though the histological changes of EAE were present in all experimental animals, NMR relaxation times and tissue specific gravity could not distinguish experimental (first attack, subsequent relapses and remissions) from control animals due to a wide range of values for each of these parameters. Although relapsing EAE in the strain 13 guinea pig has been an instructive model of MS, we have found that in vitro NMR relaxometry cannot be used to predict the presence or degree of pathological change in the nervous system of these experimental animals.     

3D spin-lock imaging of human gliomas

We investigated whether the simultaneous use of paramagnetic contrast medium and 3D on-resonance spin lock (SL) imaging could improve the contrast of enhancing brain tumors at 0.1 T. A phantom containing serial concentrations of gadopentetate dimeglumine (Gd-DTPA) in cross-linked bovine serum albumin (BSA) was imaged. Eleven patients with histologically verified glioma were also studied. T₁-weighted 3D gradient echo images with and without SL pulse were acquired before and after a Gd-DTPA injection. SL effect, contrast, and contrast-to-noise ratio (CNR) were calculated for each patient. In the glioma patients, the SL effect was significantly smaller in the tumor than in the white and gray matter both before (p = 0.001, p = 0.025, respectively), and after contrast medium injection (p < 0.001, p < 0.001, respectively). On post-contrast images, SL imaging significantly improved tumor contrast (p = 0.001) whereas tumor CNR decreased slightly (p = 0.024). The combined use of SL imaging and paramagnetic Gd-DTPA contrast agent offers a modality for improving tumor contrast in magnetic resonance imaging (MRI) of enhancing brain tumors. 3D gradient echo SL imaging has also shown potential to increase tissue characterization properties of MR imaging of human gliomas.     

Comparison of T1-weighted spin-echo and 3D T1-weighted multi-shot Echo Planar pulse sequences in imaging the brain at it.

The purpose of this study was to evaluate the ability of three dimensional T1-weighted multi-shot Echo Planar Imaging (3D T1w EPI) MR pulse sequence to provide comparable to T1w Spin Echo (SE) results in various diseases of the brain, during shorter acquisition times. Thirty-six patients (aged 30-74 years) with various indications were included in the study. All examinations were performed with a 1T MR scanner with a maximum gradient strength of 15 mT/m. The SE sequence lasted 3 min 50s and the 3D T1w EPI 59s. The quantitative analysis included number of enhancing lesions, signal-to-noise ratio of the enhancing lesions and contrast-to-noise ratio (CNR) between enhancing lesions and white matter in both sequences before and after i.v. administration of 0.1 mmol/kg gadopentetate dimeglumine. In addition, the percentage increase of enhancement was measured in each lesion of each sequence. The qualitative analysis included a) conspicuity of the lesions and b) presence of artifacts. The T1w SE sequence was significantly better compared to 3D T1w EPI in all quantitative measurements with the exception of CNR of enhancing lesions before contrast administration and the percentage enhancement. The conspicuity of the lesions did not differ between the two sequences. The EPI sequence presented with significantly more artifacts. We conclude that the 3D T1w EPI sequence could not be used instead of the conventional T1w SE, in routine imaging of the brain. Its overall diagnostic capability, could be useful only in uncooperative patients.     

Contrast-enhanced MR angiography in rats with hepatobiliary contrast agents

The aim of this animal study was to evaluate the feasibility of contrast-enhanced magnetic resonance (MR) angiography with two hepatobiliary contrast agents, Gd-DTPA-DeA and Gd-EOB-DTPA. Coronal images of the rat abdomen were acquired using a three-dimensional spoiled gradient recalled sequence before and after the administration of Gd-DTPA-DeA, Gd-EOB-DTPA, or Gd-DTPA. Four sets of postcontrast images were collected every 90 s. Contrast ratios were calculated for the abdominal aorta on the source images, and the retention index was defined as the ratio of the contrast ratio on the last imaging to that on the first postcontrast imaging. Partial minimum intensity projection (MIP) images covering the abdominal aorta were generated from the first and second postcontrast imagings, and the image quality was visually evaluated. The contrast ratio on the first postcontrast imaging was the highest for Gd-DTPA-DeA, followed by Gd-EOB-DTPA and Gd-DTPA. Retention indices were higher with Gd-DTPA-DeA than with Gd-EOB-DTPA and Gd-DTPA, implying a prolonged contrast effect with Gd-DTPA-DeA. On the MIP image from the first postcontrast imaging, delineation of the abdominal aorta tended to be better with Gd-DTPA-DeA and Gd-EOB-DTPA than with Gd-DTPA, and the difference was evident at low injection doses. Image quality for the second postcontrast imaging was higher with Gd-DTPA-DeA than with the other two agents, suggesting a longer imaging window for Gd-DTPA-DeA. In conclusion, Gd-DTPA-DeA and Gd-EOB-DTPA showed stronger contrast enhancement for the rat abdominal aorta and provided MR angiograms of higher image quality when compared with Gd-DTPA at the same injection dose. These hepatobiliary agents may make it possible to perform contrast-enhanced MR angiography even at a low injection dose.     

Active inflammation increases the heterogeneity of MRI texture in mice with relapsing experimental allergic encephalomyelitis

Inflammation modulates tissue damage in relapsing-remitting multiple sclerosis (MS) both acutely and chronically, but its severity is difficult to evaluate with conventional MRI analysis. In mice with experimental allergic encephalomyelitis (EAE, a model of MS), we administered ultra small particles of iron oxide to track macrophage-mediated inflammation during the onset (relapse) and recovery (remission) of disease activity using high field MRI. We performed MRI texture analysis, a sensitive measure of tissue regularity, and T2 assessment both in EAE lesions and the control tissue, and measured spinal cord volume. We found that inflammation was 3 times more remarkable at onset than at recovery of EAE in histology yet demyelination appeared similar across animals and disease course. In MRI, lesion texture was more heterogeneous; T2 was lower; and spinal cord volume was greater in EAE than in controls, but only MRI texture was worse at relapse than at remission of EAE. Moreover, MRI texture correlated with spinal cord volume and tended to correlate with the extent of disability in EAE. While subject to further confirmation, our findings may suggest the sensitivity of MRI texture analysis for accessing inflammation.     

Correlation between spinal cord diffusion tensor imaging and postural response latencies in persons with multiple sclerosis: A pilot study

PurposeLonger latency of postural response in multiple sclerosis (MS) may be linked to imbalance and increased likelihood of falls. It may be caused by the compromised microstructural integrity in the spinal cord, as evidenced by slowed somatosensory conduction in the spinal cord. Thus, the purpose of this study is to investigate the correlation between latency of postural responses and microstructural integrity of the cervical spinal cord, the region particularly related to the disease severity in MS, using diffusion tensor imaging (DTI) metrics.MethodsSeventeen persons with MS with mild-to-moderate disease severity were enrolled in this study. Postural response latencies of each patient were measured using electromyography of the tibialis anterior muscle (TA) and gastrocnemius muscle (GN) in response to surface perturbations. Cervical spinal cord DTI images were obtained from each patient. DTI mean, radial, axial diffusivity, and fractional anisotropy (FA) were measured between segments C4 and C6. Correlations of DTI metrics with postural response latencies, expanded disability status scale (EDSS) scores, and 25-foot walk (T25FW) were assessed using the Spearman's rank correlation coefficient at α = 0.05.ResultsLower FA was significantly correlated with longer latencies measured on right TA in response to forward postural perturbations (r = −0.51, p = .04). DTI metrics showed no significant correlations with EDSS scores (r = −0.06–0.09, p = .73–0.95) or T25FW (r = −0.1–0.14, p = .6–0.94). DTI metrics showed no significant differences between subjects with and without spinal cord lesions (p = .2–0.7).ConclusionsOur results showed a significant correlation between lower FA in the cervical spinal cord and longer latencies measured on right TA in response to forward postural perturbations in persons with MS, suggesting that impaired cervical spinal cord microstructure assessed by DTI may be associated with the delayed postural responses.     

Evaluation of CH3-DTPA-Gd (NMS60) as a new MR contrast agent: early phase II study in brain tumors and dual dynamic contrast-enhanced imaging

PURPOSE: A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations. METHODS AND MATERIALS: The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients. RESULTS: Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA. CONCLUSION: NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.     

Detection of toxoplasmic lesions in mouse brain by USPIO-enhanced magnetic resonance imaging

The objective of this study was to examine the feasibility of detecting toxoplasmic brain lesions in a mouse model of cerebral toxoplasmosis by ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI). Toxoplasmosis encephalitis was induced in Kunming mice by intracerebral injection of Toxoplasma gondii tachyzoites. T₂- and T₂*-weighted MRI was performed 1, 3, 4, 5 and 6 days after infection before USPIO injection; immediately after USPIO injection; and 24 h later. A comparison of USPIO enhancement and Gd-DTPA enhancement was made in three toxoplasmic mice 4 days after infection. Hematoxylin and eosin staining and Prussian blue staining were performed to detect inflammatory reactions and presence of iron in and around the toxoplasmic brain lesions. Nonenhanced T₂-/T₂*-weighted imaging detected few abnormalities in the brain up to 5 days. Most mice developed prominent hydrocephalus at 6 days. Gd-DTPA-enhanced imaging showed prominent enhancement of the cerebral ventricles but revealed only few space-occupying lesions in the parenchyma. USPIO-enhanced T₂*-weighted imaging showed improved detection of toxoplasmic brain lesions that were invisible to nonenhanced T₂-/T₂*-weighted imaging and gadolinium-enhanced imaging. Most of the enhancing lesions showed nodular enhancement immediately after USPIO injection, some of which changed appearance 24 h later, having a ring enhancement at the outer rim. It can be concluded that USPIO enhancement of the toxoplasmic lesions may reflect blood–brain barrier impairment and/or inflammatory reactions associated with these lesions. USPIO-enhanced imaging may be used in combination with gadolinium-enhanced imaging to provide better characterization of toxoplasmic brain lesions and, potentially, improve the differential diagnosis of toxoplasmosis encephalitis.