Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study).

BACKGROUND AND PURPOSE: Effective management of patients with brain tumors depends on accurate detection and characterization of lesions. This study aimed to demonstrate the noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors. MATERIALS AND METHODS: This multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study included 279 patients. Both contrast agents (dose = 0.1 mmol/kg of body weight) were assessed with 2 identical MRIs at a time interval of 2-14 days. The primary end point was overall lesion visualization and characterization, scored independently by 3 off-site readers on a 4-point scale, ranging from "poor" to "excellent." Secondary end points were qualitative assessments (lesion border delineation, internal morphology, degree of contrast enhancement, diagnostic confidence), quantitative measurements (signal intensity), and safety (adverse events). All qualitative assessments were also performed on-site. RESULTS: For all 3 readers, images of most patients (>90%) were scored good or excellent for overall lesion visualization and characterization with either contrast agent; and the noninferiority of gadoterate meglumine versus gadobutrol was statistically demonstrated. No significant differences were observed between the 2 contrast agents regarding qualitative end points despite quantitative mean lesion percentage enhancement being higher with gadobutrol (P < .001). Diagnostic confidence was high/excellent for all readers in >81% of the patients with both contrast agents. Similar percentages of patients with adverse events related to the contrast agents were observed with gadoterate meglumine (7.8%) and gadobutrol (7.3%), mainly injection site pain. CONCLUSIONS: The noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors was demonstrated.

Evaluation of Focal Cervical Spinal Cord Lesions in Multiple Sclerosis: Comparison of White Matter-Suppressed T1 Inversion Recovery Sequence versus Conventional STIR and Proton Density-Weighted Turbo Spin-Echo Sequences.

BACKGROUND AND PURPOSE: Conventional MR imaging of the cervical spinal cord in MS is challenged by numerous artifacts and interreader variability in lesion counts. This study compares the relatively novel WM-suppressed T1 inversion recovery sequence with STIR and proton density-weighted TSE sequences in the evaluation of cervical cord lesions in patients with MS. MATERIALS AND METHODS: Retrospective blinded analysis of cervical cord MR imaging examinations of 50 patients with MS was performed by 2 neuroradiologists. In each patient, the number of focal lesions and overall lesion conspicuity were measured in the STIR/proton density-weighted TSE and WM-suppressed T1 inversion recovery sequence groups. Independent side-by-side comparison was performed to categorize the discrepant lesions as either "definite" or "spurious." Lesion contrast ratio and edge sharpness were independently calculated in each sequence. RESULTS: Substantial interreader agreement was noted on the WM-suppressed T1 inversion recovery sequence (κ = 0.82) compared with STIR/proton density-weighted TSE (κ = 0.52). Average lesion conspicuity was better on the WM-suppressed T1 inversion recovery sequence (conspicuity of 3.1/5.0 versus 3.7/5.0, P < .01, in the WM-suppressed T1 inversion recovery sequence versus STIR/proton density-weighted TSE, respectively). Spurious lesions were more common on STIR/proton density-weighted TSE than on the WM-suppressed T1 inversion recovery sequence (23 and 30 versus 3 and 4 by readers 1 and 2, respectively; P < .01). More "definite" lesions were missed on STIR/proton density-weighted TSE compared with the WM-suppressed T1 inversion recovery sequence (37 and 38 versus 3 and 6 by readers 1 and 2, respectively). Lesion contrast ratio and edge sharpness were highest on the WM-suppressed T1 inversion recovery sequence. CONCLUSIONS: There is better interreader consistency in the lesion count on the WM-suppressed T1 inversion recovery sequence compared with STIR/proton density-weighted TSE sequences. The focal cord lesions are visualized with better conspicuity due to better contrast ratio and edge sharpness. There are fewer spurious lesions on the WM-suppressed T1 inversion recovery sequence compared with STIR/proton density-weighted TSE. The WM-suppressed T1 inversion recovery sequence could potentially be substituted for either STIR or proton density-weighted TSE sequences in routine clinical protocols.

The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study).

BACKGROUND AND PURPOSE: Gadobenate dimeglumine (MultiHance) has higher r1 relaxivity than gadoterate meglumine (Dotarem) which may permit the use of lower doses for MR imaging applications. Our aim was to compare 0.1- and 0.05-mmol/kg body weight gadobenate with 0.1-mmol/kg body weight gadoterate for MR imaging assessment of brain tumors. MATERIALS AND METHODS: We performed crossover, intraindividual comparison of 0.1-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 1) and 0.05-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 2). Adult patients with suspected or known brain tumors were randomized to Arm 1 (70 patients) or Arm 2 (107 patients) and underwent 2 identical examinations at 1.5 T. The agents were injected in randomized-sequence order, and the 2 examinations were separated by 2-14 days. MR imaging scanners, imaging sequences (T1-weighted spin-echo and T1-weighted high-resolution gradient-echo), and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images for diagnostic information (degree of definition of lesion extent, lesion border delineation, visualization of lesion internal morphology, contrast enhancement) and quantitatively for percentage lesion enhancement and lesion-to-background ratio. Safety assessments were performed. RESULTS: In Arm 1, a highly significant superiority (P < .002) of 0.1-mmol/kg gadobenate was demonstrated by all readers for all end points. In Arm 2, no significant differences (P > .1) were observed for any reader and any end point, with the exception of percentage enhancement for reader 2 (P < .05) in favor of 0.05-mmol/kg gadobenate. Study agent-related adverse events were reported by 2/169 (1.2%) patients after gadobenate and by 5/175 (2.9%) patients after gadoterate. CONCLUSIONS: Significantly superior morphologic information and contrast enhancement are demonstrated on brain MR imaging with 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate. No meaningful differences were recorded between 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate.

Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study).

BACKGROUND AND PURPOSE: Gadobutrol (Gadavist) and gadoteridol (ProHance) have similar macrocyclic molecular structures, but gadobutrol is formulated at a 2-fold higher (1 mol/L versus 0.5 mol/L) concentration. We sought to determine whether this difference impacts morphologic contrast-enhanced MR imaging. MATERIALS AND METHODS: Two hundred twenty-nine adult patients with suspected or known brain tumors underwent two 1.5T MR imaging examinations with gadoteridol or gadobutrol administered in randomized order at a dose of 0.1 mmol/kg of body weight. Imaging sequences and T1 postinjection timing were identical for both examinations. Three blinded readers evaluated images qualitatively and quantitatively for lesion detection and for accuracy in characterization of histologically confirmed brain tumors. Data were analyzed by using the Wilcoxon signed rank test, the McNemar test, and a mixed model. RESULTS: Two hundred nine patients successfully completed both examinations. No reader noted a significant qualitative or quantitative difference in lesion enhancement, extent, delineation, or internal morphology (P values = .69-1.00). One hundred thirty-nine patients had at least 1 histologically confirmed brain lesion. Two readers found no difference in the detection of patients with lesions (133/139 versus 135/139, P = .317; 137/139 versus 136/139, P = .564), while 1 reader found minimal differences in favor of gadoteridol (136/139 versus 132/139, P = .046). Similar findings were noted for the number of lesions detected and characterization of tumors (malignant/benign). Three-reader agreement for characterization was similar for gadobutrol (66.4% [κ = 0.43]) versus gadoteridol (70.3% [κ = 0.45]). There were no significant differences in the incidence of adverse events (P = .199). CONCLUSIONS: Gadoteridol and gadobutrol at 0.1 mmol/kg of body weight provide similar information for visualization and diagnosis of brain lesions. The 2-fold higher gadolinium concentration of gadobutrol provides no benefit for routine morphologic imaging.

Gadolinium contrast agents for CNS imaging: current concepts and clinical evidence.

SUMMARY: The aim of this article was to review the properties of the various gadolinium-based contrast agents used for CNS imaging along with the clinical evidence and published data that highlight the impact these different properties can have on diagnostic performance. In addition, approaches to optimizing image acquisition that take into account the different properties of specific gadolinium-based contrast agents and an extensive review of the safety profiles of the various agents are presented.

Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results.

The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and antithymocyte globulin were followed by transplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean Expanded Disability Status Scale (EDSS)=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening ≥1.0 EDSS point was 0.52 (95% confidence interval, 0.30-0.75). Five patients had an EDSS at baseline of ≤6.0; four of them had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS.

Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulus.

OBJECTIVE: To develop a non-invasive method of studying brain mechanisms involved in energy homeostasis and appetite regulation in humans by using visual food cues that are relevant to individuals attempting weight loss. DESIGN: Functional magnetic resonance imaging (fMRI) was used to compare brain activation in regions of interest between groups of food photographs. PARTICIPANTS: Ten healthy, non-obese women who were not dieting for weight loss. MEASUREMENTS: Independent raters viewed food photographs and evaluated whether the foods depicted should be eaten by individuals attempting a calorically-restricted diet. Based on their responses, we categorized photographs into 'non-fattening' and 'fattening' food groups, the latter characterized by high-caloric content and usually also high-fat or high-sugar content. Blood oxygen level-dependent (BOLD) response was measured by fMRI while participants viewed photographs of 'fattening' food, 'non-fattening' food, and non-food objects. RESULTS: Viewing photographs of fattening food compared with non-food objects resulted in significantly greater activation in the brainstem; hypothalamus; left amygdala; left dorsolateral prefrontal cortex; left orbitofrontal cortex; right insular cortex; bilateral striatum, including the nucleus accumbens, caudate nucleus, and putamen; bilateral thalamus; and occipital lobe. By comparison, only the occipital region had greater activation by non-fattening food than by object photographs. Combining responses to all food types resulted in attenuation of activation in the brainstem, hypothalamus, and striatum. CONCLUSION: These findings suggest that, in non-obese women, neural circuits engaged in energy homeostasis and reward processing are selectively attuned to representations of high-calorie foods that are perceived as fattening. Studies to investigate hormonal action or manipulation of energy balance may benefit from fMRI protocols that contrast energy-rich food stimuli with non-food or low-calorie food stimuli.

Tract-based spatial statistics of diffusion tensor imaging in adults with dyslexia.

BACKGROUND AND PURPOSE: Diffusion tensor imaging is a tool that can be used to study white matter microstructure in dyslexia. We tested the hypothesis that dyslexics have a white matter structural change (as measured by directional diffusion of water, which can be affected by disruption in white matter tracts) between brain regions that previous functional connectivity studies showed were associated with phonologic processing. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) scans were acquired from 7 healthy adult normal readers and from 14 adults with dyslexia on a 1.5T scanner. Voxelwise statistical analysis of the fractional anisotropy data were carried out by using Tract-Based Spatial Statistics to compare dyslexic subjects versus control subjects in white matter tracts. RESULTS: Significant group difference map clusters (comparing adults with and without dyslexia) occurred in specific bilateral white matter tracts within the frontal lobe, temporal lobe, occipital lobe, and parietal lobe. CONCLUSION: The DTI fractional anisotropy results in the bilateral white matter showing higher fractional anisotropy in adult control subjects compared with adults with dyslexia (relating to white matter fiber tract integrity) are consistent with our previous functional connectivity results from seed points in the bilateral inferior frontal gyrus.

Influence of PDE5 inhibitor on MRI measurement of clitoral volume response in women with FSAD: a feasibility study of a potential technique for evaluating drug response.

The purpose of this study was to determine if magnetic resonance imaging (MRI) could quantify a difference in clitoral response following administration of a vasoactive medication, in 12 women with female sexual arousal disorder (FSAD). Subjects were entered into a double-blind, randomized two-way crossover study of sildenafil 50 mg vs placebo administered 1 h prior to genital MRI. Each subject underwent two MR studies, performed while subjects viewed alternating segments of nonerotic and erotic video. MR images were analyzed for change in clitoral volume during each session. The mean change in clitoral volume for the entire group was higher in the sildenafil MRI session (1282 mm(3)) compared with placebo (849 mm(3)) but did not reach statistical significance (P=0.064). Comparison using analysis of variance between the two sessions for each individual subject revealed a significant increase in clitoral volume following sildenafil compared with placebo in 6 of 12 subjects, no significant change in either imaging session in three subjects and in three subjects, there was a robust clitoral response in both MR sessions. In conclusion, MR measurements of clitoral volume can provide an objective measure of engorgement change following a vasoactive medication in women with FSAD.

In vivo manganese MR imaging of calcium influx in spontaneous rat pituitary adenoma.

BACKGROUND AND PURPOSE: Rapid uptake of the calcium analog manganese (Mn2+) into spontaneous pituitary adenoma during MR imaging of aged rats generated the hypothesis that neuroendocrine tumors may have a corresponding increase in calcium influx required to trigger hormonal release. A goal of this study was to investigate the potential for clinical evaluation of pituitary adenoma by MR imaging combined with administration of Mn2+ (Mn-MR imaging). MATERIALS AND METHODS: Mn-MR imaging was used to characterize the dynamic calcium influx in normal aged rat pituitary gland as well as spontaneous pituitary adenoma. To confirm the validity of Mn2+ as a calcium analog, we inhibited Mn2+ uptake into the olfactory bulb and pituitary gland of normal rats by using the calcium channel blocker verapamil. Rats with adenomas received fluorodeoxyglucose-positron-emission tomography (FDG-PET) scanning for characterization of tumor metabolism. Mn2+ influx was characterized in cultured pituitary adenoma cells. RESULTS: Volume of interest analysis of the normal aged pituitary gland versus adenoma indicated faster and increased calcium influx in adenoma at 1, 3, 11, and 48 hours. Mn2+ uptake into the olfactory bulb and pituitary gland of normal rats was inhibited by calcium channel blockers and showed dose-dependent inhibition on dynamic MR imaging. FDG-PET indicated correlation between tumor energy metabolism and Mn2+ influx as well as tumor size. CONCLUSION: These results indicate that adenomas have increased activity-dependent calcium influx compared with normal aged pituitary glands, suggesting a potential for exploitation in the clinical work-up of pituitary and other neuroendocrine tumors by developing Mn-MR imaging for humans.

Sex and the brain: the role of fMRI for assessment of sexual function and response.

We briefly review the technique of functional brain imaging and its application in the assessment of the sexual response in men and women.

Static bone cavity of the mandible: Computed tomography findings with histopathologic correlation.

PURPOSE: To review computed tomography (CT) findings of histopathologically examined static bone cavities in order to determine whether an additional pathogenesis may play a role in this disease. MATERIAL AND METHODS: Four patients with histopathologically examined static bone cavities were included in this retrospective study. Location, appearance of bone remodeling, tissue characteristics, and contrast enhancement of the cavity were assessed on CT images. CT findings were then compared with the histopathological findings. RESULTS: Static bone cavity was found in the lingual molar region in three patients and in the lingual cuspid region of the mandible in one patient. Both fatty and soft tissues were present in the cavities of all four patients. Attenuation of the soft tissue in the cavities was found to be different from that of the submandibular gland. The soft tissue showed enhancement with contrast-enhanced CT in three patients. For all patients, the histopathologic content of the static bone cavity included fat, soft tissue, and abnormal vasculature. The thickened vein wall in the abnormal vasculature was observed. Aberrant tissue of the submandibular gland was not found in any of the static bone cavities. CONCLUSION: Contrast enhancement of the soft tissue on the contrast-enhanced CT images suggests the presence of vasculature in the cavities. Histopathological examination confirmed the presence of fatty tissue and dilated abnormal vessels, and the absence of salivary gland tissue in the cavities. These findings show that vascular structures are prominent in tissues found in static bone cavities.

Functional brain imaging using a long intravenous half-life gadolinium-based contrast agent.

PURPOSE: We describe a technique for functional MR imaging (fMRI) with high spatial and temporal resolution using a long intravascular half-life gadolinium-based contrast agent, MS-325. METHODS: All fMRI measurements used a rat model of sensory cortex activation with forepaw electrical stimulation under alpha-chloralose anesthesia. Standard blood oxygen level-dependent (BOLD) fMRI measurement was initially performed. MS-325 was then intravenously administered and a MS-325 fMRI measurement was performed by using a 3D gradient-echo sequence. RESULTS: We found that a dose of 0.1 mmol/kg MS-325 produced adequate signal intensity changes in rat sensory cortex to demonstrate activations. Using a boxcar stimulation pattern with a standard correlation analysis, the locations of the most significantly activated voxels (ie, highest Z score) in the MS-325 and BOLD fMRI measurements were not significantly different. CONCLUSIONS: MS-325 fMRI has the advantage of using a T1-weighted sequence, rather than the highly T2*-weighted sequences used in other common fMRI techniques. This could reduce the susceptibility artifacts associated with fMRI.

BOLD-fMRI of PTZ-induced seizures in rats.

PURPOSE: To develop a non-invasive method for exploring seizure initiation and propagation in the brain of intact experimental animals. METHODS: We have developed and applied a model-independent statistical method--Hierarchical Cluster Analysis (HCA)--for analyzing BOLD-fMRI data following administration of pentylenetetrazol (PTZ) to intact rats. HCA clusters voxels into groups that share similar time courses and magnitudes of signal change, without any assumptions about when and/or where the seizure begins. RESULTS: Epileptiform spiking activity was monitored by EEG (outside the magnet) following intravenous PTZ (IV-PTZ; n=4) or intraperitoneal PTZ administration (IP-PTZ; n=5). Onset of cortical spiking first occurred at 29+/-16 s (IV-PTZ) and 147+/-29 s (IP-PTZ) following drug delivery. HCA of fMRI data following IV-PTZ (n=4) demonstrated a single dominant cluster, involving the majority of the brain and first activating at 27+/-23s. In contrast, IP-PTZ produced multiple, relatively small, clusters with heterogeneous time courses that varied markedly across animals (n=5); activation of the first cluster (involving cortex) occurred at 130+/-59 s. With both routes of PTZ administration, the timing of the fMRI signal increase correlated with onset of EEG spiking. CONCLUSIONS: These experiments demonstrate that fMRI activity associated with seizure activity can be analyzed with a model-independent statistical method. HCA indicated that seizure initiation in the IV- and IP-PTZ models involves multiple regions of sensitivity that vary with route of drug administration and that show significant variability across animal subjects. Even given this heterogeneity, fMRI shows clear differences that are not apparent with typical EEG monitoring procedures, in the activation patterns between IV and IP-PTZ models. These results suggest that fMRI can be used to assess different models and patterns of seizure activation.

Efficiency of transfection and localization of superparamagnetic iron oxide particles in neural progenitor cells using two methods.

Stem cells represent a potentially revolutionary therapy for neurological pathologies but for which a thorough investigation of cell behavior in the living nervous system has yet to be performed. Contrast-enhanced cell tracking with magnetic resonance imaging can enable this investigation by introducing superparagmagnetic iron oxide (SPIO) particles within the cell membrane. Before magnetically labeled cells can be observed in vivo, it is essential to maximize SPIO transfer into the cell and to fully understand the localization of the contrast agent in mature neural cells. For practical applications, a quantitative evaluation of labeled cells before implantation will allow in vivo assertions. In this study, we present a comparison between two methods for magnetic transfection of neural progenitor cells: the hemmaglutinating virus of Japan envelope (HVJ-E) as a viral vector and a liposomal reagent. We show that HVJ-E is a more efficient vehicle of cell transfection using quantitative evaluation and that the iron content per cell can be predicted using a simple, automated image analysis of stained, labeled cells. Image analysis is also used in this study to show that the contrast agent is distributed in the axon after differentiation, an important aspect of understanding cell tracking in vivo.

Multimodal imaging of somatosensory evoked cortical activity.

Somatosensory evoked cortical activity is well investigated in both fMRI and MEG/EEG. Investigation with functional magnetic resonance spectroscopic (fMRS) imaging is relatively new and provides a means to image the metabolic activity of the brain. We for the first time combined fMRS, fMRI, MEG and EEG. This provides information about the metabolic, hemodynamic and electrical activity of the brain and also the verification of one imaging modality with the other. The dipolar source localized from the EEG/MEG data is in the vicinity of the fMRI activation site and also in the same area where lactate consumption is high as measured with fMRS imaging.

MRI of female genital and pelvic organs during sexual arousal.

We utilized contrast enhanced magnetic resonance imaging (MRI) to delineate the anatomy of the female genital and pelvic organs during sexual arousal. Eleven healthy pre-menopausal women and eight healthy post-menopausal women underwent MRI of the pelvis while watching an erotic video. A 1.5 Tesla MR system was used to produce T1-weighted images following administration of MS-325, a gadolinium-based blood pool contrast agent. Selected structural dimensions and enhancement were measured prior to and during sexual arousal. In both pre- and post-menopausal subjects, vestibular bulb and labia minora width increased with arousal. Enhancement measurements increased in the bulb, labia minora and clitoris in both pre- and post-menopausal subjects, and in the vagina in pre-menopausal subjects. There were no marked changes in size or enhancement of the labia majora, urethra, cervix, or rectum during sexual arousal in pre- or post-menopausal subjects. Using MRI, we observed specific changes in the female genitalia and pelvic organs with sexual arousal, in both pre- and post-menopausal women. MRI can potentially provide detailed anatomical information in the assessment of female sexual function, particularly with regard to changes in blood flow.

Brain structural abnormalities in young children with autism spectrum disorder.

OBJECTIVE: To explore the specific gross neuroanatomic substrates of this brain developmental disorder, the authors examine brain morphometric features in a large sample of carefully diagnosed 3- to 4-year-old children with autism spectrum disorder (ASD) compared with age-matched control groups of typically developing (TD) children and developmentally delayed (DD) children. METHODS: Volumes of the cerebrum, cerebellum, amygdala, and hippocampus were measured from three-dimensional coronal MR images acquired from 45 children with ASD, 26 TD children, and 14 DD children. The volumes were analyzed with respect to age, sex, volume of the cerebrum, and clinical status. RESULTS: Children with ASD were found to have significantly increased cerebral volumes compared with TD and DD children. Cerebellar volume for the ASD group was increased in comparison with the TD group, but this increase was proportional to overall increases in cerebral volume. The DD group had smaller cerebellar volumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement bilaterally that was proportional to overall increases in total cerebral volume. There were similar findings of cerebral enlargement for both girls and boys with ASD. For subregion analyses, structural abnormalities were observed primarily in boys, although this may reflect low statistical power issues because of the small sample (seven girls with ASD) studied. Among the ASD group, structural findings were independent of nonverbal IQ. In a subgroup of children with ASD with strictly defined autism, amygdalar enlargement was in excess of increased cerebral volume. CONCLUSIONS: These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.

Carotid atherosclerotic plaque: noninvasive MR characterization and identification of vulnerable lesions.

Measurement of vessel stenosis by using ultrasonography or angiography remains the principal method for determining the severity of carotid atherosclerosis and the need for endarterectomy. The ipsilateral stroke rate, however--even in patients with severely stenotic vessels--is relatively low, which suggests that the amount of luminal narrowing may not represent the optimal means of assessing clinical risk. As a result, some patients may undergo unnecessary surgery. Improved imaging techniques are, therefore, needed to enable reliable identification of high-risk plaques that lead to cerebrovascular events. High-spatial-resolution magnetic resonance (MR) imaging has been described as one promising modality for this purpose, because the technique allows direct visualization of diseased vessel wall and can be used to characterize the morphology of individual atherosclerotic carotid plaques. The purpose of this report is to review the current state of carotid plaque MR imaging and the use of carotid MR to evaluate plaque morphology and composition.

Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study.

High-resolution magnetic resonance imaging (MRI) with flow suppression not only provides useful information on luminal and wall areas of the carotid artery but also can identify the principal tissue components of the carotid atherosclerotic plaque. The effects of intensive lipid-lowering therapy on these MRI tissue characteristics were examined in patients with coronary disease (CAD). Eight CAD patients who have been receiving intensive lipid-lowering treatment (niacin 2.5 g/d, lovastatin 40 mg/d, and colestipol 20 g/d) for 10 years in the Familial Atherosclerosis Treatment Study (FATS) follow-up were randomly selected from among 60 such treated patients. Eight CAD patients who were matched to the treated patients for age (+/-3 years), baseline low density lipoprotein (+/-5 mg/dL), and triglycerides (+/-50 mg/dL) but who had never been treated with lipid-lowering drugs were selected as controls. For each of these 32 carotid arteries, luminal and plaque areas were measured by planimetry, in a blinded protocol, from the magnetic resonance image that showed most plaque. Fibrous tissue, calcium, and lipid deposits were identified on the basis of established criteria. Plaque composition was estimated as a fraction of total planimetered area. Patients treated with 10-year intensive lipid-lowering therapy, compared with control subjects, had significantly lower low density lipoprotein cholesterol levels (84 versus 158 mg/dL, respectively; P<0.001) and higher high density lipoprotein cholesterol levels (51 versus 37 mg/dL, respectively; P<0.001). As a group, treated patients, compared with untreated control subjects, had a smaller core lipid area (0.7 versus 10.2 mm(2), respectively; P=0.01) and lipid composition (1% versus 17%, respectively). Group differences in luminal area (55 [treated] versus 44 [control] mm(2), P=NS) and plaque area (58 [treated] versus 64 [control] mm(2), P=NS) tended to favor treatment. MRI appears useful for estimating carotid plaque size and composition. Hyperlipidemic CAD patients frequently (97%) have at least moderate (>/=40% area stenosis) carotid plaque. In this case-control study, prolonged intensive lipid-lowering therapy is associated with a markedly decreased lipid content, a characteristic of clinically stable plaques.