Intracerebral administration of heat-inactivated Staphylococcus epidermidis enhances oncolysis and prolongs survival in a 9L orthotopic gliosarcoma model.

BACKGROUND/AIMS: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. METHODS: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. RESULTS: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Naïve 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. CONCLUSION: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics.

MRI of coronary wall remodeling in a swine model of coronary injury using an elastin-binding contrast agent.

BACKGROUND: The extracellular matrix (ECM) plays an important role in the pathogenesis of atherosclerosis and in-stent restenosis. Elastin is an essential component of the ECM. ECM degradation can lead to plaque destabilization, whereas enhanced synthesis typically leads to vessel wall remodeling resulting in arterial stenosis or in-stent restenosis after stent implantation. The objective of this study was to demonstrate the feasibility of MRI of vascular remodeling using a novel elastin-binding contrast agent (BMS-753951). METHODS AND RESULTS: Coronary injury was induced in 6 pigs by endothelial denudation and stent placement. At day 28, delayed-enhancement MRI coronary vessel wall imaging was performed before and after injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). Two days later, DE-MRI was repeated after administration of BMS-753951. Contrast-to-noise-ratio and areas of enhancement were determined. Delayed-enhancement MRI with BMS-753951 caused strong enhancement of the aortic, pulmonary artery, and injured coronary artery walls, whereas Gd-DTPA did not. Delayed-enhancement MRI of the stented coronary artery with BMS-753951 yielded a 3-fold higher contrast-to-noise-ratio when compared with the balloon-injured and control coronary artery (21±6 versus 7±3 versus 6±4; P<0.001). The area of enhancement correlated well with the area of remodeling obtained from histological data (R(2)=0.86, P<0.05). CONCLUSIONS: We demonstrate the noninvasive detection and quantification of vascular remodeling in an animal model of coronary vessel wall injury using an elastin-specific MR contrast agent. This novel approach may be useful for the assessment of coronary vessel wall remodeling in patients with suspected coronary artery disease. Further studies in atherosclerotic animal models and degenerative ECM disease are now warranted.

Evaluation of an active vena cava filter for MR imaging in a swine model.

PURPOSE: To evaluate the feasibility of magnetic resonance (MR) imaging-guided placement of an active vena cava filter (AVCF) in a swine model, the effectiveness of the system in filtering thrombi, and the detection of thrombi with MR imaging. MATERIALS AND METHODS: This study was approved by the government committee on animal investigations. An AVCF tuned to the Larmor frequency of a 1.5-T MR unit was placed in the inferior vena cava (IVC) of seven pigs under real-time MR imaging guidance. Steady-state free precession sequences with four different flip angles (90°, 40°, 25°, and 15°), T1-weighted turbo spin-echo sequences with two flip angles (90° and 15°), and black-blood proton-density-weighted sequences with a flip angle of 90° were performed before and after filter placement. In six cases, extracorporeally produced thrombi were injected through the femoral access to test filter function. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were assessed before and after filter deployment and compared by using the signed-rank test. RESULTS: All AVCFs were successfully deployed. Significant differences (P < .05) in the SNR and CNR of the IVC were found before and after AVCF placement and between sequences with different flip angles. Intravenous thrombi were caught in all cases and clearly depicted with MR imaging. On black-blood proton-density-weighted images, high-signal-intensity thrombi inside the filter were clearly detectable without any overlaying artifacts. CONCLUSION: MR imaging-guided deployment and monitoring of an AVCF is feasible. The AVCF enhances the SNR and CNR, resulting in clear depiction of thrombi inside the filter without the need for contrast material. Design modifications for improved intracaval fixation and retrieval of the prototype AVCF will be required.

Combined interventional stroke therapy using intracranial stent and local intraarterial thrombolysis (LIT).

INTRODUCTION: Supported by results of the ECASS III study, intravenous rt-PA thrombolysis is considered a standard therapy for acute stroke within 4.5 h. Still under debate is the use of a more aggressive treatment as that of local intraarterial thrombolysis (LIT) or combining intravenous administration of recombinant tissue plasminogen activator (rt-PA) followed by LIT (bridging concept). Mechanical thrombus removal devices and effective flow achievement by stenting are reported to increase the recanalization rate and patient outcome. Newer reports showed the use of intracranial stents as the latest trend-setting technique. A combined approach hereby appears to achieve the best results consisting of pharmacologic thrombolysis, manual aspiration devices and stenting. We employed a novel removable stent as a new approach in acute stroke, aiming to make the intraarterial thrombolysis through an enhanced thrombus contact surface more effective and to reduce the effective revascularisation time with the possibility of stent removal after re-opening the occluded vessel. METHODS: We describe four cases with acute stroke in the anterior and posterior circulation using a newer self-expandable removable stent (Solitaire™ AB) combined with LIT performed in the 'bridging technique', occasionally supported by additional thrombus aspiration. RESULTS: In all cases, we directly achieved after stenting an effective revascularization with fast recanalization time when using stent implantation first. Stenting was always technically successful without complications. CONCLUSION: The easy handling of a removable stent in stent-assisted revascularization combined with thrombolysis (i.v./i.a.) is a newly described technique for acute stroke treatment, which join immediate mechanical recanalization, postulated improved thrombolysis and the possibility of stent removing.

Registration of coronary venous anatomy to the site of the latest mechanical contraction.

OBJECTIVE: Cardiac resynchronization therapy (CRT) provides a therapeutic option for patients with congestive heart failure (CHF). There is evidence that the optimal pacing site (OIS) is vicinal to the region of the latest contraction (RLC). However, the RLC is not identified routinely to guide lead implantation to the coronary venous system (CVS). The aim of this study was: (i) to develop a software over-imposing CVS-anatomy on parametric images of left ventricular dyssynchrony in a 3D-format obtained from computed tomography (CT) and cardiac magnetic resonance imaging (MRI); and (ii) to apply this 3D-software for analysing the possible correlation between functional/ clinical improvement and the distance between final implantation site (FIS) and RLC. METHODS AND RESULTS: In 20 CHF-patients (11 men, 65.6 +/- 6.8 y, ejection fraction (EF): 27.5 +/- 6.1%) CRT-leads were implanted; follow-up included echocardiographic and exercise evaluation. The OIS and the FIS were noted on 3D-registrations and the distances OIS-RLC and FIS-RLC measured.The target vessel was reached in 14 cases. NYHA class and EF improved significantly with a low rate of non-responders of 3 (15%) (EF) and 4 (20%) (NYHA). Image registration was possible in all patients. Post-process 3D-analysis revealed no correlation between the distance FIS-RLC and functional or echocardiographic improvements.There was a trend towards a shorter distance FIS-RLC in patients classified as responders (EF). NYHA class improved significantly better in patients with target vessel implantation. CONCLUSIONS: Registration of CT/MRI-images enables efforts to reach the RLC by preoperative identification of corresponding veins. Larger randomized trials must define the definite therapeutic benefit.

The impact of early-onset cannabis use on functional brain correlates of working memory.

Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations.

Altered parahippocampal functioning in cannabis users is related to the frequency of use.

RATIONALE: Converging lines of evidence suggest an association between cannabis use and impaired episodic memory as well as related associative learning. These deficits have been associated with the duration, frequency, and age of onset of cannabis use. However, it remains unclear whether these parameters of use differently impact memory-related hippocampal functioning. METHODS: Forty-two cannabis users were examined by means of functional magnetic resonance imaging while they encoded and retrieved face-profession associations. Region of interest analysis was subsequently used to compare (para-)hippocampal functioning in users with (1) a longer and shorter duration of use, (2) a higher and lower frequency of use, and (3) an earlier and later onset. To further separate the effects of these parameters of use on performance and (para-)hippocampal activity, linear regression analysis was applied. RESULTS: Compared to low-frequency users, high-frequency users displayed stronger blood oxygenation level-dependent response during encoding in the left parahippocampal gyrus. No differences were obvious for the groups separated according to duration of use or an earlier and later onset of use. Linear regression analysis confirmed the association between a higher frequency of use and increased activity in the left parahippocampal gyrus. CONCLUSIONS: Our findings suggest that the frequency of use might have a particular critical impact on intact parahippocampal functioning in cannabis users. Increased activity within the encoding-related network might reflect functional compensation to maintain cognitive functioning.

Cervical hemorrhage due to spontaneous rupture of the superior thyroid artery: Case report and review of the literature.

BACKGROUND: Beneath the different reasons for cervical masses, a spontaneous hemorrhage presents a rare and life-threatening condition. METHODS AND RESULTS: We present the rare case of a 62-year-old man who was presented with a dramatically enlarging cervical mass causing respiratory distress because of upper airway compression. An endotracheal intubation was lifesaving and avoided tracheotomy. A CT scan revealed a hematoma in the region of the left external carotid artery. An emergency angiography embolized a ruptured branch of the superior thyroid artery and surgery evacuated the hematoma. We discuss the rarity of the condition, reasons for a spontaneous rupture of the artery, and the diagnostic and treatment strategy. In addition, we review the literature on spontaneous thyroid artery hemorrhages, which, up to now, have been described only for the inferior thyroid artery. CONCLUSION: We conclude that the optimal management for cases of cervical hematoma is intubation, diagnosis, and angiography before surgery.

Flow targeted 3D steady-state free-precession coronary MR angiography: comparison of three different imaging approaches.

PURPOSE: To compare 3 different flow targeted magnetization preparation strategies for coronary MR angiography (cMRA), which allow selective visualization of the vessel lumen. MATERIAL AND METHODS: The right coronary artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D radial steady-state free-precession (SSFP) cMRA sequence with 3 different magnetization preparation schemes was performed referred to as projection SSFP (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP (double-inversion preparation, selective labeling of the aorta, 1 data set), and inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1 data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast-to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel length and vessel sharpness were analyzed. RESULTS: All cMRA sequences were successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP allowed for selective visualization of the coronary arteries with excellent background suppression. Scan time was doubled in projection SSFP because of the need for subtraction of 2 data sets. In inflow SSFP, background suppression was limited to the tissue included in the inversion volume. Projection SSFP (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7) and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat): 24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5; P < 0.05 for both). Longest visible vessel length was found with projection SSFP (79.5 mm +/- 18.9; P < 0.05 vs. LoReIn) whereas vessel sharpness was best in inflow SSFP (68.2% +/- 4.5%; P < 0.05 vs. LoReIn). Consistently good image quality was achieved using inflow SSFP likely because of the simple planning procedure and short scanning time. CONCLUSION: Three flow targeted cMRA approaches are presented, which provide selective visualization of the coronary vessel lumen and in addition blood flow information without the need of contrast agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness and may prove useful as a fast and efficient approach for assessing proximal and mid vessel coronary blood flow, whereas requiring less planning skills than projection SSFP or LoReIn SSFP.

Thrombus imaging with fibrin-specific gadolinium-based MR contrast agent EP-2104R: results of a phase II clinical study of feasibility.

PURPOSE: To determine the feasibility of detecting thrombi using a fibrin-specific gadolinium-based magnetic resonance imaging contrast agent, EP-2104R. METHODS: Subjects with confirmed thrombus in the venous system (n = 14), or in the heart, or arterial system (n = 38) were enrolled. Patients were imaged before and at various times following a 4 mumol/kg intravenous bolus injection of EP-2104R: <1 hour (N = 16), 2 to 6 hours (N = 36), and/or 20 to 36 hours (N = 33). Images were assessed by investigators at each site and by a single reader not affiliated with the sites to determine whether thrombi were visible, not visible, or further enhanced with EP-2104R. A subset of data was analyzed quantitatively by measuring a signal intensity relative to background tissue. RESULTS: Overall, 29 thrombi were visible before contrast administration, 3 of 14 in the venous system, and 26 of 38 in the arteries and heart. Thrombi generally enhanced in signal after EP-2104R injection, and an additional 7 were visualized. After contrast, 4 of 14 thrombi were visible in the venous system, and 32 of 38 in the arteries and heart. Thrombi were more conspicuous when imaged at 2 to 6 hours post EP-2104R compared with within 1 hour, because of lower blood background. Quantitatively, the post: pre signal intensity ratio was 1.90 at 2 to 6 hours post injection (standard deviation = 1.08, N = 20, P < 0.001); and 2.04 (standard deviation = 1.29, N = 19, P < 0.0025) for the 20 to 36 hours time point. There were no serious adverse events considered related to study drug. CONCLUSION: EP-2104R enhanced magnetic resonance imaging detects thrombi not readily visible in precontrast screening and gives additional enhancement of thrombi that are visible in precontrast imaging.

Molecular magnetic resonance imaging of myocardial perfusion with EP-3600, a collagen-specific contrast agent: initial feasibility study in a swine model.

BACKGROUND: Cardiac magnetic resonance (MR) perfusion imaging during the first pass after intravenous administration of extracellular contrast agents is hampered by the spatial and temporal resolution achievable and by the artifacts seen in ultrafast MR imaging. Furthermore, time-consuming quantitative data analysis is often added. The use of molecular MR imaging with a target-specific contrast agent with perfusion-dependent binding to myocardium may enable prolonged visualization of perfusion defects and thus may help to overcome limitations of currently used first-pass extracellular MR imaging. EP-3600 is a new gadolinium-containing molecular contrast agent that binds reversibly to myocardial collagen. METHODS AND RESULTS: A significant but nonocclusive coronary artery stenosis was modeled in 7 domestic swine with an undersized MR-compatible balloon positioned in the left anterior descending artery as verified by x-ray angiography. Two animals died before contrast injection as a result of arrhythmias. In 5 swine, high-spatial-resolution gradient echo imaging (approximately 1 x 1 mm(2) in-plane resolution) was performed before and 5, 20, 40, and 60 minutes after intravenous administration of 12.3 micromol/kg EP-3600. Contrast was administered during stress induced by an infusion of 250 mumol x kg(-1) x min(-1) adenosine. Yb-DTPA was administered simultaneously for comparison of myocardium-to-plasma ratios. Images were assessed subjectively by 2 investigators, and signal-to-noise and contrast-to-noise ratios over time were calculated. Normal myocardium showed a significant signal-to-noise ratio increase during the entire examination time. In all animals (n=5), the perfusion defect in the left anterior descending artery territory could be visualized with a high contrast-to-noise ratio for at least 20 minutes after contrast injection. A significantly higher myocardium-to-plasma ratio was found for EP-3600 compared with the control agent Yb-DTPA (0.85+/-0.26 versus 0.22+/-0.08, respectively; P<0.01). CONCLUSIONS: EP-3600 is a new molecular MR imaging contrast agent that binds to the myocardium and enables prolonged, high-contrast, high-spatial-resolution visualization of myocardial perfusion defects.

Molecular magnetic resonance imaging of deep vein thrombosis using a fibrin-targeted contrast agent: a feasibility study.

PURPOSE: To evaluate the value of a fibrin-specific MR contrast agent (EP-2104R; EPIX Pharmaceuticals) for detection of deep vein thrombosis (DVT) and monitoring of percutaneous intervention for treatment. MATERIALS AND METHODS: In 6 domestic swine, DVT was induced in an iliac/femoral vein using an occlusion-balloon catheter and subsequent injection of thrombin. The occluded vessels were recanalized by mechanical thrombectomy using a Fogarty catheter and an Arrow rotating thrombectomy device. Magnetic resonance imaging of the pelvis and lung was repeated 4 times (before and after DVT induction, after contrast agent administration, and after intervention) using a 1.5-T whole-body XMR system (ACS-NT, Philips Medical Systems, Best, NL). The visualization of the thrombi and contrast-to-noise ratio (CNR) was assessed. RESULTS: EP-2104R allowed selective visualization of thrombi with accurate determination of the extent of DVT with high contrast (CNR: 65.3 +/- 17.2). After intervention, dislodged thrombus fragments were selectively visualized in the lung (CNR: 27.9 +/- 9.3). CONCLUSIONS: Molecular magnetic resonance imaging using fibrin-specific MR contrast agent EP-2104R allowed for selective visualization of DVT and monitoring of percutaneous intervention.

An MR guidewire based on micropultruded fiber-reinforced material.

A novel fiber-reinforced material for the realization of MR guidewires, made using a newly-developed production process, is presented. The MR-safe artificial material provides a high stiffness and torque and allows the production, in a large range of sizes, of nonmetallic MR guidewires with similar mechanical properties as conventional metallic guidewires. Based on this material, a passively visualized MR guidewire has been developed, and was found to conform to existing standards on mechanical stability. Handling and steerability were evaluated in animal studies and were found to be comparable with conventional metallic guidewires. X-ray visibility is provided by a BaSO(4)- and tungsten-doped jacket. A hydrophilic coating improves sliding properties and hemocompatibility.

Time-resolved 3D MR angiography of the foot at 3 T in patients with peripheral arterial disease.

OBJECTIVE: The objective of our study was to prove the feasibility and clinical relevance of fast contrast-enhanced time-resolved 3D MR angiography (MRA) with submillimeter spatial resolution at a high magnetic field strength. SUBJECTS AND METHODS: Twenty-one patients (five women, 16 men; mean age +/- SD, 65 +/- 14 years) were examined on a 3-T whole-body MR system with an 8-element phasedarray coil for preoperative evaluation of the pedal arterial system and assessment of the visualized vessels to serve as a graft touch-down site in pedal bypass surgery. Time-resolved 3D MRA of the foot was performed after automatic injection of 0.2 mmol/kg of gadobenate dimeglumine using a sagittal gradient-echo T1-weighted sequence (TR/TE, 4.2/1.6; flip angle, 30 degrees ; field of view, 290 mm; matrix, 352; 120 slices; slice thickness, 0.8 mm) with a spatial resolution of 0.8 x 0.8 x 1.6 mm reconstructed to 0.6 x 0.6 x 0.8 mm and a temporal resolution of 3.9 seconds using keyhole and sensitivity-encoding (SENSE) technology (SENSE factors: 4 in anteroposterior direction and 2 in right-left direction). Dynamic subtractions and rotating maximum intensity projections were calculated. The original image data sets were transferred to a dedicated workstation for objective signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) analysis of the arteries. Subjective image analysis regarding image quality and diagnostic findings was performed by two radiologists in consensus. RESULTS: In all patients, images of diagnostic quality were obtained. Despite the known limitations regarding signal intensity measurements in images acquired with the use of parallel imaging technique, SNR and CNR proved to be excellent, with mean +/- SD values of 294 +/- 158 and 248 +/- 144, respectively. Although most of the patients had diabetic foot syndrome with arteriovenous shunting, the arteries and the potential vessel for bypassing could be clearly separated from the veins in each case due to the temporal information given by our study. The ability to reliably discriminate arteries from veins is of high clinical relevance in planning pedal bypass surgery. CONCLUSION: Fast contrast-enhanced time-resolved 3D MRA of the foot at 3 T is feasible and of high clinical value for the preoperative evaluation of the arterial supply of the foot.

Local re-inversion coronary MR angiography: arterial spin-labeling without the need for subtraction.

PURPOSE: To implement a double-inversion bright-blood coronary MR angiography sequence using a cylindrical re-inversion prepulse for selective visualization of the coronary arteries. MATERIALS AND METHODS: Local re-inversion bright-blood magnetization preparation was implemented using a nonselective inversion followed by a cylindrical aortic re-inversion prepulse. After an inversion delay that allows for in-flow of the labeled blood-pool into the coronary arteries, three-dimensional radial steady-state free-precession (SSFP) imaging (repetition/echo time, 7.2/3.6 ms; flip angle, 120 degrees, 16 profiles per RR interval; field of view, 360 mm; matrix, 512, twelve 3-mm slices) is performed. Coronary MR angiography was performed in three healthy volunteers and in one patient on a commercial 1.5 Tesla whole-body MR System. RESULTS: In all subjects, coronary arteries were selectively visualized with positive contrast. In addition, a middle-grade stenosis of the proximal right coronary artery was seen in one patient. CONCLUSION: A novel T1 contrast-enhancement strategy is presented for selective visualization of the coronary arteries without extrinsic contrast medium application. In comparison to former arterial spin-labeling schemes, the proposed magnetization preparation obviates the need for a second data set and subtraction.

MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients.

This study was an initial phase II trial in humans of molecular magnetic resonance (MR) imaging for improved visualization of thrombi in vessel territories potentially responsible for stroke using a new fibrin-specific contrast agent (EP-2104R). Eleven patients with thrombus in the left ventricle (n = 2), left or right atrium (n = 4), thoracic aorta (n = 4) or carotid artery (n = 1) as verified by an index examination (ultrasound, computed tomograpy, or conventional MR) were enrolled. All MR imaging was performed on 1.5 T whole-body MR-system using an inversion-recovery black-blood gradient-echo sequence. The same sequence was performed before and 2-6 h after low-dose intravenous administration of 4 mumol/kg EP-2104R. Two investigators assessed image quality and signal amplification. Furthermore, contrast-to-noise ratios (CNR) between the clot and the blood pool/surrounding soft tissue before and after administration of the contrast agent were compared using Student's t-test. MR imaging and data analysis were successfully completed in 10 patients. No major adverse effects occurred. On enhanced images, thrombi demonstrated high signal amplification, typically at the clot surface, with a significantly increased contrast in comparison to the surrounding blood pool and soft tissue (CNR for clot vs. blood pool, unenhanced and enhanced: 6 +/- 8 and 29 +/- 14; CNR for clot vs. soft tissue, unenhanced and enhanced: 0 +/- 4 and 21 +/- 13; P < 0.01 for both comparisons). EP-2104R allows for molecular MR imaging of thrombi potentially responsible for stroke. High contrast between thrombus and surrounding blood and soft tissues can be achieved with enhanced imaging.