Marcus Katoh

In Vivo Magnetic Resonance Imaging of Coronary Thrombosis Using a Fibrin-Binding Molecular Magnetic Resonance Contrast Agent

Background—The advent of fibrin-binding molecular magnetic resonance (MR) contrast agents and advances in coronary MRI techniques offers the potential for direct imaging of coronary thrombosis. We tested the feasibility of this approach using a gadolinium (Gd)-based fibrin-binding contrast agent, EP-2104R (EPIX Medical Inc), in a swine model of coronary thrombus and in-stent thrombosis. Methods and Results—Ex vivo and in vivo sensitivity of coronary MR thrombus imaging was tested by use of intracoronarily delivered Gd-DTPA–labeled fibrinogen thrombi (n=6). After successful demonstration, in-stent coronary thrombosis was induced by x-ray–guided placement of thrombogenic-coated, MR-lucent stents (n=5). After stent placement, 60 &mgr;mol of EP-2104R was injected via the left main coronary artery. Free-breathing, navigator-gated 3D coronary MR angiography and thrombus imaging were performed (1) before and after stent placement and (2) before and after EP-2104R. Thrombi were confirmed by x-ray angiography and autopsy. Fibrinogen thrombi: 5 of 6 intracoronarily delivered Gd-labeled fibrinogen clots (≈250 &mgr;mol/L Gd) were visible on MRI and subsequently confirmed by x-ray angiography. In-stent thrombi: in-stent thrombosis was observed in all stents after EP-2104R. Four of 5 thrombi were confirmed by x-ray angiography. Chemical analysis of 2 thrombi demonstrated 99 to 147 &mgr;mol/L Gd. Conclusions—We demonstrate the feasibility of MRI of coronary thrombus and in-stent thrombosis using a novel fibrin-binding molecular MR contrast agent. Potential applications include detection of coronary in-stent thrombosis or thrombus burden in patients with acute coronary syndromes.

Molecular Magnetic Resonance Imaging of Coronary Thrombosis and Pulmonary Emboli With a Novel Fibrin-Targeted Contrast Agent

Background—The differential diagnosis of acute chest pain is challenging, especially in patients with normal ECG findings, and may include coronary thrombosis or pulmonary emboli. The aim of this study was to investigate the novel fibrin-specific contrast agent EP-2104R for molecular targeted MR imaging of coronary thrombosis and pulmonary emboli. Methods and Results—Fresh clots were engineered ex vivo from human blood and delivered in the lungs and coronary arteries of 7 swine. Subsequent molecular MR imaging was performed with a navigator-gated free-breathing and cardiac-triggered 3D inversion-recovery black-blood gradient-echo sequence before and after systemic administration of 7.5 &mgr;mol/kg EP-2104R. Two swine served as the control group. MR images were analyzed by 2 investigators, and contrast-to-noise ratio and gadolinium concentration in the clots were assessed. Before contrast media application, no thrombi were visible. After contrast administration, all 32 pulmonary emboli, 3 emboli in the right heart, and 5 coronary thrombi were selectively visualized as white spots with a mean contrast-to-noise ratio of 32±19. The average gadolinium concentration from all 3 types of thrombi was 144±79 &mgr;mol/L. Conclusions—Molecular MR imaging with the fibrin-targeted contrast-agent EP-2104R allows selective visualization of acute coronary, cardiac, and pulmonary thrombi.

Molecular magnetic resonance imaging of atrial clots in a swine model.

Background—The detection and differentiation of intracardiac masses is still challenging and may include neoplasms and thrombi. The aim of this study was the investigation of a targeted, fibrin-specific contrast agent (EP-2104R) for molecular targeted magnetic resonance imaging (MRI) of left atrial clots. Methods and Results—Chronic human thrombi were surgically implanted in the left atrial appendage of 5 swine. Molecular MRI was performed with a navigator-gated, free-breathing, cardiac-triggered 3D inversion-recovery, black-blood, gradient-echo sequence before and after systemic administration of 4 &mgr;mol/kg EP-2104R. MR images were analyzed by 2 investigators, and the contrast-to-noise ratio was calculated. Location of clots was confirmed by autopsy, and the gadolinium concentration in the clots was assessed. Before contrast agent administration, thrombi were not visible on black-blood MR images. After contrast administration, all atrial clots (n=5) were selectively visualized as white spots with a high contrast-to-noise ratio (clot/blood, 29.7±8.0). The gadolinium concentration in the clots averaged 74±45 &mgr;mol/L. Conclusions—The fibrin-specific MR contrast agent EP-2104R allows for selective and high-contrast visualization of left atrial clots by means of molecular targeted MRI.

A feasibility study of contrast enhancement of acute myocardial infarction in multislice computed tomography: comparison with magnetic resonance imaging and gross morphology in pigs.

Introduction:Late enhancement magnetic resonance imaging (MRI) of myocardial infarction (MI) is clinically established. There are no reports on MI assessment using state-of-the-art multislice CT technology. For this reason, animal experiments were conducted to examine the applicability of contrast-enhanced ECG-gated multislice computed tomography (MSCT) for the detection of acute MI. The results were correlated with MRI and postmortem tissue staining. Material and Methods:Acute MI was induced in 14 pigs by balloon occlusion of the LAD. In 8 animals, the LAD was reperfused after 45 minutes. In 6 animals, the LAD was permanently blocked. MR imaging was performed 15 minutes after the administration of 0.2 mmol Gd-DTPA/kg/bodyweight. Subsequently, 16-slice MSCT was performed at various timepoints after injecting 120 mL of iodinated contrast medium. 2,3,5-Triphenyltetrazolin-chloride (TTC) staining was acquired for all hearts investigated. Correlation analysis was applied to compare the area of MI derived from MRI, MSCT, and TTC. The reperfused infarcts were compared with the nonreperfused infarcts using an unpaired t test. Results:Mean infarct area as measured by TTC staining was 18.3% ± 7.8% of the left ventricular area. Good correlation of the spatial extent of the infarcted area was found for TTC and MRI as well as for TTC and MSCT data obtained 5 minutes postcontrast injection. MSCT imaging demonstrated a significant difference in density (P < 0.001) between nonreperfused (47.0 ± 6.6 HU) and reperfused (116.4 ± 19.8 HU) infarction. Conclusion:In our pilot study, contrast-enhanced MSCT was feasible to assess myocardial viability in pigs. MSCT also affords differentiation of nonreperfused and reperfused acute MI. MI sizes derived from MSCT imaging correlate well to those obtained with MRI and TTC.

Molecular MR imaging of human thrombi in a swine model of pulmonary embolism using a fibrin-specific contrast agent

Objective:Molecular targeted MR imaging of human clots material in a model of pulmonary embolism using a fibrin-specific magnetic resonance imaging contrast agent (EP-2104R, EPIX Pharmaceuticals, Cambridge, MA). Material and Methods:Fresh ex vivo engineered thrombi (human blood) and human clots removed from patients were delivered in 11 swine. Molecular MR imaging with a 3D gradient-echo [3D fast field echo (3DFFE)] sequence and a navigator-gated and cardiac-triggered 3D inversion-recovery black-blood gradient-echo sequence (IR) was performed before thrombus delivery, after thrombus delivery but before contrast media application, and 2 hours after i.v. administration of 4 &mgr;mol/kg EP-2104R. MR images were analyzed by 2 investigators and contrast-to-noise ratio (CNR) was assessed. Thrombi were removed for assessment of gadolinium (Gd) concentration. Results:Only after contrast media application were pulmonary emboli [freshly engineered thrombi (n = 23) and human clot material removed from patients (n = 25)] visualized as white foci on MR images. CNR was 13 ± 3 (ex vivo engineered clot) and 22 ± 9 (patient clot material) for the fast field echo (FFE)-sequence and 29 ± 9 (ex vivo engineered clot) and 43 ± 18 (patient clot material) for the IR-sequence, respectively. A high Gd concentration in the clots was found (82 ± 43 &mgr;M for the freshly engineered and 247 ± 44 &mgr;M for the clots removed from patients, respectively). Conclusions:EP-2104R allows for molecular MR imaging of human clot material in the pulmonary vessels of a swine model.

In vivo safe catheter visualization and slice tracking using an optically detunable resonant marker

The purpose of this study was to test the in vivo feasibility of safe automatic catheter tracking based on an optically detunable resonant marker installed on the catheter tip, and also to test the compatibility of this approach with guidewire materials. The design of the resonant marker and the integration into the real‐time MR environment is described. The catheter was used for real‐time MR‐guided catheterization of the aorta, left ventricle, and carotid in two swine. For in‐plane visualization, the marker was repeatedly detuned. For automatic slice tracking, a projection difference measurement including detuning was interleaved with the imaging sequence. In vitro experiments were conducted to investigate the RF‐safety of the marker and the effect of the guidewires on the signal intensity. For all orientations the marker provided excellent in vivo contrast using a radial steady‐state free‐precession sequence. Flashing of the marker by repetitive tuning/detuning further improved the in‐plane visualization. Automatic slice tracking during real‐time imaging was successfully performed. The plastic guidewires did not interfere with the marker, and detuning by guidewires containing nitinol could be compensated. In conclusion, automatic slice tracking as well as excellent in‐plane visualization can be achieved with this approach and it is safe with respect to RF transmission. Magn Reson Med 52:860–868, 2004.

Free-breathing renal magnetic resonance angiography with steady-state free-precession and slab-selective spin inversion combined with radial k-space sampling and water-selective excitation.

The impact of radial k‐space sampling and water‐selective excitation on a novel navigator‐gated cardiac‐triggered slab‐selective inversion prepared 3D steady‐state free‐precession (SSFP) renal MR angiography (MRA) sequence was investigated. Renal MRA was performed on a 1.5‐T MR system using three inversion prepared SSFP approaches: Cartesian (TR/TE: 5.7/2.8 ms, FA: 85°), radial (TR/TE: 5.5/2.7 ms, FA: 85°) SSFP, and radial SSFP combined with water‐selective excitation (TR/TE: 9.9/4.9 ms, FA: 85°). Radial data acquisition lead to significantly reduced motion artifacts (P < 0.05). SNR and CNR were best using Cartesian SSFP (P < 0.05). Vessel sharpness and vessel length were comparable in all sequences. The addition of a water‐selective excitation could not improve image quality. In conclusion, radial k‐space sampling reduces motion artifacts significantly in slab‐selective inversion prepared renal MRA, while SNR and CNR are decreased. The addition of water‐selective excitation could not improve the lower CNR in radial scanning. Magn Reson Med 53:1228–1233, 2005.

Effect of varying slice thickness on coronary calcium scoring with multislice computed tomography in vitro and in vivo.

Objectives:To compare coronary calcium scoring results (calcium volume, calcium mass, Agatston score, and number of lesions) of different slice thicknesses using a 16-slice CT (MSCT) scanner. Materials and Methods:A nonmoving anthropomorphic thorax phantom with calcium cylinders of different sizes and densities was scanned 30 times with repositioning applying a standardized retrospectively ECG-gated MSCT (SOMATOM Sensation 16; Siemens, Forchheim, Germany) scan protocol: collimation 12 × 0.75 mm, tube voltage 120 kV, effective tube current time-product 133 mAseff. Fifty patients (29 male; age 57.2 ± 8.4 years) underwent a nonenhanced scan applying the same scan protocol. Two image sets (effective slice thicknesses 3 mm and 1 mm) were reconstructed at 60% of the RR interval. Image noise was measured in both studies. Calcium volume, calcium mass and Agatston score were calculated using a commercially available software tool. Results:Due to increased image noise in thinner slices, calcium scoring in all scans was performed applying a scoring threshold of 350 HU. In the phantom study, 1-mm slices showed significantly higher scoring results in respect to calcium volume (+8.2%), calcium mass (+12.5%), and Agatston score (+5.3%) (all P < 0.0001). In the patient study, 27 patients had coronary calcifications in 3-mm slices, and 31 patients had coronary calcifications in 1-mm slices. Thinner slices showed significantly higher scoring results in respect to volume (+47.1%), mass (+47.2%), and Agatston score (+29.7%) (all P < 0.0001). Conclusions:When comparing 3-mm and 1-mm slices in coronary calcium scoring in MSCT, thinner slices lead to significantly increased scoring results.

MR coronary vessel wall imaging: Comparison between radial and spiral k-space sampling

To compare radial and spiral k‐space sampling in navigator‐gated ECG‐triggered three‐dimensional (3D) coronary vessel wall imaging.

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.