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Diagnosis of Patent Foramen Ovale Using Contrast-Enhanced Dynamic MRI: A Pilot Study

¹ Department of Cardiovascular MRI, Cardiovascular Center Bethanien, Im Pruefling 17, D-60389 Frankfurt/Main, Germany.
² German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ University of Oxford Centre for Cardiovascular Magnetic Resonance, John Radcliffe Hospital, Oxford, England.

Received April 15, 2004; accepted after revision June 14, 2004.

 
Address correspondence to O. K. Mohrs (o.mohrs{at}ccb.de).

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
OBJECTIVE. The aim of this study was to evaluate the feasibility of dynamic contrast-enhanced MRI for detection of patent foramen ovale.

SUBJECTS AND METHODS. Fifteen patients with and five patients without patent foramen ovale underwent transesophageal echocardiography and MRI, which were performed during the Valsalva maneuver. Grading results (grade 0, no patent foramen ovale and grades 1–3, minor to major enhancement due to intracardiac shunt) were assessed visually. Signal-intensity curves in the left atrium and in a pulmonary vein served to underline the diagnosis.

RESULTS. The diagnoses of all patients with (15/15) and without patent foramen ovale (5/5) were correct compared with the findings of the reference transesophageal echocardiography. In 12 (60%) of 20 patients, the grading scores were identical, and in four (20%) of 20 patients, the scores differed by more than one grade. Overall, there was a good correlation of grading scores (r = 0.7, p < 0.05). Using signal-intensity curves, we found that the patients with patent foramen ovale showed an additional signal peak in the left atrium before the enhancement of the pulmonary vein because of an intracardiac shunt. In three of 15 patients with patent foramen ovale, an atrial septal aneurysm was correctly diagnosed.

CONCLUSION. This pilot study shows that MRI is a new noninvasive method to detect patent foramen ovale and atrial septal aneurysm. A grading is possible but warrants further investigation regarding its predictive value and impact on treatment strategies.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patent foramen ovale (PFO) is a known cause of cerebral strokes or transient ischemic attacks due to paradoxical embolism. Diagnosis and treatment are required to prevent further cerebral events.

In patients without cardiac symptoms, the incidence of PFO is 34% during the first three decades and declines with age, as seen in autopsy studies [1]. The annual recurrence rate of cerebral stroke or transient ischemic attacks for patients with PFO is about 3.5% [2, 3]. PFOs with large shunts have a higher risk than those with small shunts [4]. Recent studies show a higher incidence for cerebral strokes if the PFO is associated with an atrial septal aneurysm [5–8]. Therefore, an ideal method should show both diagnoses, PFO and atrial septal aneurysm.

Contrast-enhanced transesophageal echocardiography (TEE) is considered the clinical reference to detect PFO and atrial septal aneurysm [9]. This method, however, is semiinvasive. Recently, MRI has been established in many cardiovascular applications, particularly because of the latest developments of hardware and ultrafast sequences [10]. The purposes of this study were threefold: to investigate the feasibility of MRI to noninvasively and visually detect PFO and atrial septal aneurysm using contrast-enhanced MRI, to evaluate the use of signal–time curves to diagnose the shunt across the PFO using the Valsalva maneuver, and to correlate grading of PFO using contrast-enhanced MRI in comparison with TEE.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Study Population
Fifteen consecutive patients with a PFO detected on contrast-enhanced TEE were enrolled for contrast-enhanced MRI (five women; mean age, 49 ± 14 years [SD]) after written informed consent was obtained (Table 1). The study was approved by the local review board. Contrast-enhanced MRI was performed within 1 week of TEE. Twelve of these 15 patients had a history of cerebral events, including transient ischemic attacks, amaurosis fugax, or strokes. The indications for TEE in the remaining patients with PFO were recurrent peripheral emboli (one patient) and suspected PFO at routine transthoracic echocardiography. The control group consisted of five patients (one woman; mean age, 59 ± 13 years) without PFO confirmed by TEE. In these patients, TEE was performed to exclude atrial thrombi.

TEE
TEE was performed with a 5-MHz phased multiplane probe (Vingmed System Five, GE Healthcare). We used 0.02 mg of orally administered lidocaine (Xylocain Pumpspray, AstraZeneca) for local pharyngeal anesthesia. The contrast agent (D-galactose, Echovist, Schering) was administered as a bolus of 10 mL into an antecubital vein during a Valsalva maneuver. Right-to-left shunting was graded in consensus by an experienced cardiologist and radiologist as follows [11]: grade 0, no contrast agent passed from the right to the left atrium; grade 1, 3–9 microbubbles passed from the right to the left atrium; grade 2, 10–30 microbubbles passed from the right to the left atrium; and grade 3, greater than 30 microbubbles passed from the right to the left atrium (opacified left atrium due to bright contrast). The presence of atrial septal aneurysm was defined as a protrusion of the atrial septum into the left or right atrium of greater than 10 mm.

MRI
Contrast-enhanced MRI was performed on a 1.5-T MRI system (Magnetom Sonata Maestro Class, Siemens Medical Solutions). For signal detection, the combination of a six-channel body phased-array coil and a two-channel spine phased-array coil was used. ECG signal was received from an external system (Magnitude 3150, InVivo Research).

An ECG-gated segmented true fast imaging with steady-state free precession (FISP)–cine sequence (TR/TE, 2.7/1.2; temporal resolution, 34 msec; voxel size, 1.7 x 1.3 x 6.0 mm³) served for detection of atrial septal aneurysms in a stack of contiguous horizontal long-axis views and short-axis planes. The presence of atrial septal aneurysm was assessed in consensus by an experienced cardiologist and radiologist who were blinded to the TEE diagnosis.

Contrast-enhanced perfusion analysis was performed during the Valsalva maneuver using 10 mL of gadopentetate dimeglumine (Magnevist, Schering) followed by a 20-mL saline solution, administered into an antecubital vein. The infusion rate was 6 mL per second. Two slices of a saturation-recovery true FISP sequence (TE, 2.7 msec; inversion time, 217 msec; flip angle, 50°; temporal resolution, 832 msec; matrix, 144 x 256; voxel size, 1.8 x 1.4 x 6.5 mm³) were positioned in the horizontal long and short axis, which showed the optimal view of the fossa ovalis chosen from the cine studies. For each slice, 40 consecutive images were acquired, one per heart cycle.

Contrast-enhanced perfusion studies were analyzed by reviewers who were blinded to the TEE diagnosis and grade of PFO and consisted of the following aspects: visual assessment grading of PFO and interpretation of signal–time curves to diagnose PFO.

Signal–time curves were generated using the program Mean Curve (Siemens Medical Solutions). Two regions of interest (ROIs) were placed in a pulmonary vein and the left atrium. ROIs were manually fitted to every image without changing the size. The atrial ROIs were drawn close to the atrial septum, but inclusion of pixels from the right atrium was carefully avoided. The signal–time curves were normalized to baseline signal (second image) for each ROI. The single data points represented the percentage of the baseline signal. PFO grading for contrast-enhanced MRI was performed on the basis of the grading system as follows: grade 0, no contrast enhancement in the left atrium before the contrast agent reached the pulmonary veins; grade 1, only slight contrast enhancement close to the atrial septum without enhancement of the entire left atrium before the contrast agent reached the pulmonary veins; grade 2, only slight contrast enhancement in the left atrium before the contrast agent reached the pulmonary veins; and grade 3, bright contrast enhancement in the left atrium before the contrast agent reached the pulmonary veins.

Statistical Analysis
Data presentation and statistical analyses performed in this study were chosen to avoid the assumption of a normal distribution. Data are given as medians (quartile 1, quartile 3, minimum, maximum). TEE and contrast-enhanced MRI grading scores were correlated using the Spearman's rank correlation. The Mann-Whitney U test for unpaired variables was used to test for differences between patients with and without PFO regarding time points of peaks in the signal–time curves and their signal intensities. A p value of less than 0.05 was considered statistically significant. All computations were performed with SPSS software, version 11.5 (Statistical Package for the Social Sciences) for Windows (Microsoft).

Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Visual Diagnosis of PFO and Atrial Septal Aneurysm
PFO was identified visually in all 15 patients using contrast-enhanced MRI. In all five control patients, PFO could be correctly excluded by visual contrast-enhanced MRI assessment. For all 15 patients with PFO evaluated, an early contrast enhancement due to intracardiac right-to-left shunting was present in the left atrium before the contrast agent reached the pulmonary veins (Figs. 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 1M, and 1N, Movies 1 and 2). The prevalence of atrial septal aneurysm in our study population of PFO patients was 20% (3/15) detected on TEE. Three of 15 patients were correctly identified using the contrast-enhanced MRI (Figs. 2A and 2B, Movie 3). Neither false-negative nor false-positive diagnoses were made with MRI.

View larger version (120K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (66K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (74K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (83K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (83K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1E. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (93K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1F. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (92K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1G. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1H. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (74K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1I. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (80K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1J. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1K. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (86K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1L. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (98K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1M. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (101K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1N. —32-year-old man with patent foramen ovale grade 3 on transesophageal echocardiography and grade 3 on MRI. Figures 1A and 1H show anatomy using true fast imaging with steady-state free precession–cine sequence in horizontal long axis (A) and short axis (H) at atrial level. Figures 1B–1G and 1I–1N show temporal sequence of contrast-enhanced dynamic perfusion imaging during Valsalva maneuver. Figures 1B and 1I show baseline signal without enhancement. Figures 1C and 1J show enhancement of right atrium (RA). Figures 1D and 1K show enhancement of entire left atrium (LA) due to right-to-left shunting (arrows) before enhancement of pulmonary vein (PV). Figures 1E and 1L show signal decrease in LA representing dip after first initial peak back to baseline. Figures 1F and 1M show enhancement of PV and second signal peak in LA. Figures 1G and 1N show enhancement of aorta. RV = right ventricle, LV = left ventricle, RV = right ventricle, Ao = aorta, PA = pulmonary artery.

View larger version (160K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —32-year-old man with atrial septal aneurysm (arrow) on MRI. Typical bulging of atrial septum is shown toward left atrium (LA) in horizontal long axis (A) and toward right atrium (RA) in short axis (B).

View larger version (142K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —32-year-old man with atrial septal aneurysm (arrow) on MRI. Typical bulging of atrial septum is shown toward left atrium (LA) in horizontal long axis (A) and toward right atrium (RA) in short axis (B).

Grading of PFO
All five control patients without PFO depicted on TEE were correctly categorized as having grade 0 on contrast-enhanced MRI. Overall, seven (47%) of 15 patients with PFO (grades 1–3) were given grades identical to those of the reference TEE. The classifications of four patients differed by one grade between the diagnosis based on TEE and that based on contrast-enhanced MRI, and classifications of the remaining four patients differed by two grades. Among the patients with PFO, there was no systematic underestimation or overestimation of the grades. Taking the control patients with grade 0 into this calculation, we found that 12 (60%) of 20 patients were categorized identically and 16 (80%) of 20 were graded with a maximal grade difference of one (Table 2). The correlation for the 20 participants was good (r = 0.7, p < 0.05) but was poor without the grade 0 patients (r = 0.19, not significant).

Diagnosis of PFO Using Signal–Time Curves
In the control group, the signal–time curves showed a peak of 514% of baseline signal in the pulmonary vein 19 sec after contrast agent administration. This peak in the pulmonary vein was followed by a single peak of 484% in the left atrium at 20 sec. In contrast to the control group, all patients with PFO showed signal–time curves with an early first peak in the left atrium of 160% of baseline signal at 7 sec. This was followed by the peak in the pulmonary vein of 486% at 17 sec. The initial peak and drop back to baseline in the left atrium were followed by a second higher peak of 517% at 19 sec. The time point and the percentage of baseline signal of the first peak in the left atrium were significantly different between the patients with PFO and controls (p < 0.002). Differences between the time point and the percentage of baseline signal of the peak in the pulmonary vein were not significant. On the basis of the presence or absence of an early first signal peak in the left atrium followed by a second peak in the left atrium, the diagnoses of all patients with and without PFO were correct as compared with the reference TEE diagnoses (Figs. 3 and 4).

View larger version (12K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3. —Graph of signal–time curve in 32-year-old man with patent foramen ovale shows early initial signal peak (arrow) in left atrium () followed by second higher peak before peak in pulmonary vein ().

View larger version (10K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4. —Graph of typical signal–time curve in 26-year-old man without patent foramen ovale shows single peak in left atrium () at almost same time as peak in pulmonary vein ().

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
This pilot study could show the feasibility of reliably diagnosing PFO and atrial septal aneurysms using contrast-enhanced MRI. Various MRI techniques have been used to visualize atrial septal defects [12]. The combination of visualization of morphologic defects and the analysis of functional consequences (e.g., shunt detection) allows the diagnosis of an atrial septal defect [13, 14]. Until now, the diagnosis of PFO has not been possible using MRI because of insufficient spatial and temporal resolution and the absence of a measurable shunt volume.

TEE is the current clinical reference for the diagnosis of PFO, which correlated well in autopsy studies [15, 16]. The major drawbacks of TEE are its semiinvasiveness and the inability to acquire more than one imaging plane during the administration of the contrast agent.

The results presented in this study underline the potential of contrast-enhanced MRI to noninvasively reliably detect PFO either by visual assessment or by computation of signal–time curves in the pulmonary vein and the left atrium. The advantage of signal-time-curve analysis is the clear-cut differentiation of contrast enhancement due to right-to-left shunting in the left atrium from pulmonary flow. This is not possible with TEE and may cause false-positive results in the rare, but important, case of a pulmonary arteriovenous malformation.

PFO patients with huge shunts have been shown to have a higher risk for paradoxical embolisms than those with small shunts [17, 18]. This finding forms the rationale for grading PFO because therapeutic strategies could be based on the severity of the shunt across the PFO despite the lack of widely accepted guidelines [19]. We show a good correlation between the grading scores using TEE and contrast-enhanced MRI including all patients with and without PFO. If the control group of patients without PFO (grade 0) was excluded from the correlation analysis, then the correlation was poor. We suspect that the discrepancies might reflect the intraindividual variability of performing the Valsalva maneuver, which is the most effective way to induce a right-to-left atrial shunting [20]. If the patient does not perform a Valsalva maneuver correctly, a PFO can be missed [21]. Therefore, deep sedation might alter the cooperation required to perform this maneuver and thus bias the degree of shunt observed. This might pose a problem in patients who cannot tolerate the transesophageal probe or the contrast-enhanced MRI investigation without IV sedation.

Another cause for the limited correlation in grading scores for both techniques in PFO patients can be sought in the limited number of imaging planes despite the much-improved temporal and spatial resolution. We used two different imaging planes in the present study. For a more reliable quantification, a 3D volume would be needed. This is currently available for neither TEE nor contrast-enhanced MRI. Because of the opposite anatomic position of the ostium of the inferior vena cava in relation to the fossa ovalis, a contrast injection into the femoral vein could potentially improve the evaluation of shunt size for both techniques [22].

The presence of atrial septal aneurysms in PFO patients has a major predictive value [6]. Diagnosis of atrial septal aneurysm and evaluation of PFO in one single investigation using contrast-enhanced MRI or TEE are major advantages over transcranial Doppler sonography, which can reliably detect PFO, but not atrial septal aneurysm [23]. In our study, atrial septal aneurysm in all three patients with this condition was correctly diagnosed using MRI.

Currently, contrast-enhanced MRI cannot replace TEE to exclude other potential embolic sources such as thrombus in left atrial appendage. The feasibility of contrast-enhanced MRI to exclude this embolic source was not addressed in our study and warrants further investigation. Compared with TEE, contrast-enhanced MRI examinations currently are more expensive and need a longer examination time.

This pilot study was designed to show the potential of this new application to evaluate and grade PFO and to detect atrial septal aneurysms. A larger prospective study is needed to confirm our findings and to show the predictive value of PFO grading for clinical outcome. Our initial contrast-enhanced MRI experience, however, encourages the design of studies to show the feasibility of contrast-enhanced MRI as a noninvasive technique to screen, for example, scuba divers [24].

In conclusion, this pilot study has shown that contrast-enhanced MRI can be used to reliably detect PFO and atrial septal aneurysm on the basis of the visual assessment.

Acknowledgments
 
This study contains data from the doctoral thesis by Damir Erkapic.

References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc1984; 59:17 -20[Medline]
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