Real-time MR with TrueFISP for the detection of acute pulmonary embolism: initial clinical...

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Received: 5 May 2003 Revised: 15 September 2003 Accepted: 29 October 2003 Published online: 5 December 2003 © Springer-Verlag 2003 Abstract The feasibility and diag- nostic value of real-time magnetic resonance imaging (RT-MRI) for the diagnosis of acute pulmonary embo- lism (PE) was evaluated by compar- ing RT-MRI and magnetic resonance angiography (MRA). In 39 consecu- tive patients with suspected PE real- time true fast imaging with steady- state precession (TrueFisp) was pro- spectively compared with contrast- enhanced MRA on a 1.5-T MR scan- ner. The TrueFisp sequence used al- lowed acquisition of T2-weighted images at 0.4 s per image so that the pulmonary vasculature could be visualized in three orientations in <3 min without the need for breath holding or contrast media applica- tion. Results of additional scinti- graphic pulmonary perfusion exam- inations were available from 17 pa- tients. All 39 primary RT examina- tions (100%) and 30 of 39 MRA ex- aminations (77%) were of diagnostic quality. The reasons underlying fail- ure to achieve diagnostic quality for MRA were breathing artifacts among dyspneic patients in all 9 cases. Compared with MRA, the sensitivi- ties and specificities of RT sequenc- es for PE were 93 and 100% (per ex- amination), 96 and 100% (lobar ar- tery PE), and 97 and 100% (segmen- tal artery PE), respectively. Com- pared with scintigraphy, the sensitiv- ity and specificity of RT-MRI were 83 and 100%, respectively. The MRA reached 100% sensitivity and specificity in this subgroup. The RT-MRI proved to be very robust and undisturbed by respiratory movements and patient cooperation. Its image quality assured fast diag- nostic examinations, and its sensitiv- ity and specificity, compared with MRA and scintigraphy, were suffi- cient to allow the diagnosis of acute central, lobar, and segmental PE; therefore, the emergency diagnosis of PE using RT-MRI is feasible and reliable. Keywords MR angiography · Pulmonary artery · Pulmonary embolism · Real-time imaging Eur Radiol (2004) 14:709–718 DOI 10.1007/s00330-003-2164-5 CHEST Alexander Kluge Clemens Müller Jochen Hansel Tibo Gerriets Georg Bachmann Real-time MR with TrueFISP for the detection of acute pulmonary embolism: initial clinical experience Introduction Pulmonary embolism (PE) is the third most common acute cardiovascular disease after cardiac ischemia and stroke [1]. As 1-year mortality rates from PE among treated patients is 2.5% [2], adequate, timely diagnosis is mandatory. Widely used perfusion-ventilation scintigra- phy lacks specificity [3]. While pulmonary angiography was a long-standing gold standard, its restricted avail- ability, the examination time required, the equipment and personnel demands, and a low percentage of major com- plications [4] all conspired to motivate a search for alter- natives. Spiral CT, introduced for the diagnosis of PE by Remy-Jardin et al. in 1992 [5], has become the most widely used imaging modality [6]. Multi-slice CT allows imaging at the subsegmental level [7, 8] and visualizes simultaneous diseases such as atelectasis. This makes CT a very attractive tool for the referring physician since PE A. Kluge ( ) · C. Müller · T. Gerriets G. Bachmann Department of Diagnostic Radiology, Kerckhoff Heart Center, Beneke-Strasse 2–8, 61231 Bad Nauheim, Germany e-mail: [email protected]. uni-giessen.de Tel.: +49-6032-9962420 Fax: +49-6032-9962433 J. Hansel Department of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany T. Gerriets Department of Neurology, University of Giessen, Giessen, Germany

Transcript of Real-time MR with TrueFISP for the detection of acute pulmonary embolism: initial clinical...

Page 1: Real-time MR with TrueFISP for the detection of acute pulmonary embolism: initial clinical experience

Received: 5 May 2003Revised: 15 September 2003Accepted: 29 October 2003Published online: 5 December 2003© Springer-Verlag 2003

Abstract The feasibility and diag-nostic value of real-time magneticresonance imaging (RT-MRI) for thediagnosis of acute pulmonary embo-lism (PE) was evaluated by compar-ing RT-MRI and magnetic resonanceangiography (MRA). In 39 consecu-tive patients with suspected PE real-time true fast imaging with steady-state precession (TrueFisp) was pro-spectively compared with contrast-enhanced MRA on a 1.5-T MR scan-ner. The TrueFisp sequence used al-lowed acquisition of T2-weightedimages at 0.4 s per image so that the pulmonary vasculature could bevisualized in three orientations in<3 min without the need for breathholding or contrast media applica-tion. Results of additional scinti-graphic pulmonary perfusion exam-inations were available from 17 pa-tients. All 39 primary RT examina-tions (100%) and 30 of 39 MRA ex-aminations (77%) were of diagnosticquality. The reasons underlying fail-ure to achieve diagnostic quality forMRA were breathing artifacts among

dyspneic patients in all 9 cases.Compared with MRA, the sensitivi-ties and specificities of RT sequenc-es for PE were 93 and 100% (per ex-amination), 96 and 100% (lobar ar-tery PE), and 97 and 100% (segmen-tal artery PE), respectively. Com-pared with scintigraphy, the sensitiv-ity and specificity of RT-MRI were83 and 100%, respectively. TheMRA reached 100% sensitivity andspecificity in this subgroup. The RT-MRI proved to be very robustand undisturbed by respiratorymovements and patient cooperation.Its image quality assured fast diag-nostic examinations, and its sensitiv-ity and specificity, compared withMRA and scintigraphy, were suffi-cient to allow the diagnosis of acutecentral, lobar, and segmental PE;therefore, the emergency diagnosisof PE using RT-MRI is feasible andreliable.

Keywords MR angiography · Pulmonary artery · Pulmonary embolism · Real-time imaging

Eur Radiol (2004) 14:709–718DOI 10.1007/s00330-003-2164-5 C H E S T

Alexander KlugeClemens MüllerJochen HanselTibo GerrietsGeorg Bachmann

Real-time MR with TrueFISP for the detectionof acute pulmonary embolism: initial clinical experience

Introduction

Pulmonary embolism (PE) is the third most commonacute cardiovascular disease after cardiac ischemia andstroke [1]. As 1-year mortality rates from PE amongtreated patients is 2.5% [2], adequate, timely diagnosis ismandatory. Widely used perfusion-ventilation scintigra-phy lacks specificity [3]. While pulmonary angiographywas a long-standing gold standard, its restricted avail-

ability, the examination time required, the equipment andpersonnel demands, and a low percentage of major com-plications [4] all conspired to motivate a search for alter-natives. Spiral CT, introduced for the diagnosis of PE byRemy-Jardin et al. in 1992 [5], has become the mostwidely used imaging modality [6]. Multi-slice CT allowsimaging at the subsegmental level [7, 8] and visualizessimultaneous diseases such as atelectasis. This makes CTa very attractive tool for the referring physician since PE

A. Kluge (✉) · C. Müller · T. GerrietsG. BachmannDepartment of Diagnostic Radiology,Kerckhoff Heart Center,Beneke-Strasse 2–8, 61231 Bad Nauheim,Germanye-mail: [email protected].: +49-6032-9962420Fax: +49-6032-9962433

J. HanselDepartment of Cardiology,Kerckhoff Heart Center,Bad Nauheim, Germany

T. GerrietsDepartment of Neurology,University of Giessen,Giessen, Germany

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represents just one major differential diagnosis for tho-racic pain or dyspnea. Due to its robustness, the accuracyof CT for diagnosing PE is regarded as being higher thanthat of magnetic resonance angiography (MRA) [9]. In-herent disadvantages of CT angiography (CTA) includeexposure to ionizing radiation and the necessity to ad-minister iodinated contrast media. For this reason, MRAhas long been scrutinized as a procedure for diagnosingPE.

The MRA, although delivering a performance close tosingle-slice CT [10, 11], has played a limited role inevaluating PE up to now. Its lack of availability and lim-ited patient access, as well as long examination time,have restricted its clinical use. Patients had to be able tosustain breath-holding periods of 15–27 s which limitedindications to non-emergency diagnostics.

As real-time MR (RT-MRI), because of its design, isnot susceptible to motion artifacts, this technique obvi-ates the aforementioned disadvantages and appearspromising for the evaluation of acute PE. True fast imag-ing with steady-state precession (TrueFISP, also calledsteady-state free precession) RT sequences produce pre-dominantly T2-weighted contrasts which allow inherentdiscrimination of embolic material and patent pulmonaryvessels/blood. We therefore evaluated for the first timethe diagnostic value of RT TrueFISP MRI in patientswith suspected acute PE and compared it with contrast-enhanced MRA and perfusion scintigraphy. The poten-tial of RT-MRI for detecting non-embolic thoracic dis-eases was also evaluated.

Materials and methods

Patients

Thirty-nine consecutive in-house patients with suspected PE wereprospectively examined using MR imaging (17 men and 22 wom-en; mean age 57±13 years). They were referred to us by cardiolo-gists. Suspicion arose from clinical symptoms, D-dimer tests,echocardiography, and duplex phlebosonography. Due to the focusof the radiology department on cardiac MRI, no CT scanner, andtherefore no CTA, was available, and scintigraphy was availableonly during the daytime; thus, MRI was used as a primary diag-nostic modality.

Informed consent was obtained, clinical condition permitting.The clinical condition of patients with suspected PE was gradedaccording to the following scale: stage I, asymptomatic or milddyspnea; stage II, severe dyspnea and agitation; and stage III, se-vere dyspnea and decreased blood pressure.

Protocol

All patients with suspected PE were examined on a 1.5-T MRscanner (Magnetom Sonata, Siemens, Erlangen, Germany). Thepatients were placed within the MRI scanner, in the supine posi-tion, head first, with arms alongside the thorax. A quadraturephased-array coil was positioned on the patients’ chest. For con-trast media application, a 20-G peripheral intravenous line wasplaced in an antecubital vein and was connected to a power injec-

tor (Spectris, Medrad, Pittsburgh, Pa.). Monitoring of blood oxy-gen saturation and ECG was applied if required by the clinicalcondition, but not routinely, since no cardiac-gated sequenceswere used. Mechanically ventilated patients could be examined ifa respiration bag was used, since the strong external magneticfield of this MR scanner model interfered even with MR-compati-ble mechanical respirator models. Examination time was assessedretrospectively using DICOM tags for series, acquisition, and im-age time. Times required for the RT-MRI protocol and for thecomplete imaging protocol are given as mean±standard deviation(SD).

Real-time MRI

A non-cardiac-gated RT TrueFISP single-shot sequence similar topublished techniques [12, 13] was used. Apart from the cardiacgating, basic image characteristics were similar to those of cardi-ac-gated TrueFISP sequences described previously [14, 15]. Pa-rameters were adapted for minimal time of acquisition whilemaintaining a high spatial resolution (TR 3.1 ms, TE 1.5 ms, flipangle 59°). Bandwidth was increased to 1000 Hz for shorter acqui-sition times. In-folding artifacts in the coronal plane caused by arectangular field of view (FOV) were permitted in order toachieve an acquisition time of below 0.5 s/image. Artifacts dis-turbed peripheral parts of the thorax, but not central, lobar, or seg-mental pulmonary artery (PA) branches. Since the acquisition ofcontiguous overlapping slices was not possible, two blocks of con-tiguous, non-overlapping slices were acquired interleaved, bothblocks covering the same volume shifted by 50% slice thickness.The combination of both block’s slices resulted in the desired con-tiguous 50% overlapping slices. No extinction artifacts were de-tected in precursor studies or in the present study. Fat suppressionwas not applied so that a longer acquisition time could be avoided.

The RT TrueFISP sequence was applied according to the fol-lowing protocol: (a) 100 contiguous slices in a coronal orientation,FOV 360 mm, 256×192 pixels, slice thickness 4 mm, 2-mm over-lap, and acquisition time 0.52 s per slice; (b) 100 contiguous slicesin a sagittal orientation, FOV 360 mm, 256×180 pixels, slicethickness 4 mm, 2-mm overlap, and acquisition time 0.45 s perslice; (c) 120 contiguous slices in a transverse orientation, FOV340 mm, 256×156 pixels, slice thickness 3 mm, 1.5-mm overlap,and acquisition time 0.4 s per slice.

The slices covered the following regions to guarantee stan-dardized comprehensive imaging of the pulmonary vasculature inthree orthogonal projections: transverse orientation from the apexof the lung to the portal vein; coronal orientation from the manu-brium sterni to the spinous process; and sagittal orientation fromthe right to the left medial clavicular line. Individual adaptation ofslice geometry or position could be discarded since all three or-thogonal stacks of slices covered both lungs entirely and standardhead-first patient positioning placed the main PA in the center ofthe FOV and stack; thus, the sequences could be started immedi-ately without adaptation or modification of any parameters. Imag-es could be evaluated online after a delay of 1–2 s.

MRA

The RT images were used for proper planning of the consecutiveMRA. Before starting contrast-enhanced (CE) MRA, a sagittal bo-lus timing sequence was performed after administration of 2-mlgadopentate dimeglumine (Gd-DTPA, Magnevist, Schering, Ber-lin, Germany) at 3 ml/s followed by a 30-ml saline flush at 3 ml/s.The delay was determined as the time from injection to peak pul-monary trunk enhancement minus 4 s.

The MRA was performed using a 3D fast low-angle shot(FLASH) sequence (TR 3.2 ms, TE 1.4 ms, flip angle 25°, fat sat-uration applied to avoid hampering infolding artifacts from the pa-

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tients arms). A coronal FOV of 340 mm (512×384 pixels, 72 parti-tions, voxel size 0.7×1.2×1.5 mm) covered the pulmonary vascula-ture in 22 s. Twenty-millileters Gd-DTPA were injected at 3 ml/safter the previously determined delay followed by a 20-ml salineflush. Two sequential MRA breath-hold measurements were per-formed. A 10-s break allowed the patient to resume respiration.The second measurement served as backup if bolus timing, motionartifacts, or patient cooperation compromised the image quality ofthe first 3D data set.

Nuclear medicine

Perfusion lung scans were acquired additionally in 17 patientswithin 24 h of the respective MRI examination. Two-dimensionalplanar lung scans with eight standard projections using an Ecom180° dual-head camera (Siemens, Erlangen, Germany) were per-formed in 11 patients. Six patients were examined using a singlephoton emission computed tomography (SPECT) technique. Thedata of a 3D SPECT perfusion lung scintigraphy were transformedinto 64 transverse slices per examination. Tc-99m macroaggregat-ed albumin with an activity of 148 MBq was used as the radio-pharmaceutical.

Image interpretation

All examinations were evaluated by two radiologists (A.K., G.B.),and final diagnosis was made on the basis of consensus. Each pul-monary, lobar, and segmental artery of every patient was assessedseparately with both sequence techniques. Every vessel was de-picted on at least two RT images per plane, i.e., five to seven im-ages per segmental vessel, and the evaluation referred to the plane,and the images showing the vascular wall and lumen without arti-facts. Concordant results from two planes were required to con-firm an RT-MRI finding.

For final evaluations, RT-MRI sequences and MRA examina-tions were evaluated separately to avoid any recall bias: firstly, allRT sequences from all patients were interpreted in random orderbefore all the MRA data sets were evaluated. The MRA were as-sessed on non-reconstructed images as well as on multiplanar re-constructed (MPR) images and seldom on maximum intensity pro-jection (MIP) images. The time required for RT image interpreta-tion was assessed during this final evaluation and rounded off tothe nearest completed 5-min period.

Signal-to-noise ratio [SNR; mean signal intensity (SI)/SD ofSI], SI ratio (SI of surrounding blood/SI of embolic material), andcontrast-to-noise ratio (CNR; SI of blood−SI of embolic materi-al/noise) were calculated for all 5 central, all 18 left lobar, and all22 segmental emboli of left and right S10. Values given aremeans±SD.

Subsegmental arteries, although usually depicted in RT-MRIand MRA, were not evaluated. The lingula stem of the left seg-mental arteries four and five, although anatomically part of the leftupper lobe, was categorized as a lobar artery due to its size and or-igin. Segment seven (left medial basal or cardiac segment) of theleft lung was not evaluated separately but regarded as part of theanteromedial segment, S8, of the left lung.

Both MRA and RT-MRI data sets were evaluated for coinci-dental mediastinal or pulmonary parenchymal findings not relatedto PE.

Diagnostic quality

Pulmonary artery imaging was classified on RT-MRI and MRA asbeing “non-diagnostic”, “diagnostic without thrombus,” and “di-agnostic with thrombus.” Diagnostic quality was assumed if oneof the following criteria were met: (a) discrimination of vessel

wall and vessel lumen or thrombotic material was possible; or (b)the in-plane course of the vessel allowed simultaneous judgmentof the relative blood flow (RT-MRI) or contrast enhancement(MRA) in different parts of the vessel.

Non-diagnostic quality of a single vessel was assumed if thevessel could not to be identified or exclusion of PE was not possi-ble due to blurred vascular representation. Non-diagnostic qualityof the examination was assumed if more than three lobar arteriesor more than half the segmental arteries failed to achieve diagnos-tic quality.

Diagnostic criteria

Diagnosis of PE was established if (consistent with conventionalpulmonary angiography and CTA criteria) either (a) thrombuscould be directly visualized, or (b) cutoff of pulmonary vessel, or(c) abrupt changes in signal intensity during the course of PA weredetected. These criteria applied for MRA and RT-MRI.

Statistical analysis

Vessels in an area with non-diagnostic image quality were excludedfrom analysis. A finding was classified as false negative if throm-bus was clearly visible in MRA but not visible in RT-MRI. Al-though detectable, no discrimination was made between thromboticmaterial adherent to the vessel wall or floating freely in the vascu-lar lumen, since determination of thrombus age was not an objec-tive of this study. Evaluation was made at the segmental, lobar, andcentral PA level and per examination. Sensitivity and specificity, aswell as positive and negative predictive values (PPV, NPV), werecalculated using MRA as a reference standard. For this reason, ex-aminations with non-diagnostic MRA sequences (9 of 39, 23%)had to be excluded from the evaluation. Due to the high percentageof non-diagnostic MRA examinations, a separate preliminary anal-ysis used direct visualization of thrombotic material as “prima facieevidence” and, therefore, RT-MRI for reference purposes. The sub-group of patients with perfusion lung scans was additionally evalu-ated using scintigraphy as a reference standard.

Percentage of diagnostic quality at different clinical stages wasanalyzed using the chi-square test for linear trends.

Results

Clinical stage I of suspected PE was diagnosed in 23 of39 patients, stage II in 11 examinations, and stage III in5 patients.

Thirty-nine examinations were performed using RT-MRI and MRA. The examination time for RT-MRI was209±25 s. The complete imaging protocol, including lo-calization, bolus timing, preparation and MRA, required11 min 10 s±1 min 57 s.

Diagnostic quality

Non-diagnostic PA depiction of RT sequences wascaused by poor blood signal intensity in segmental arte-ries and flow artifacts in central and lobar PA. Evalua-tion of segmental vessels on RT images was simpler forvessels with a long in-plane course or for vessels depict-ed as being artifact free in a transverse section.

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Direct thrombus visualization allowed lobar and cen-tral embolism to be easily detected on RT images bybrowsing the coronal stack of images, referring to trans-verse and sagittal orientation for confirmation. At thesegmental level, images had to be evaluated in all threeorientations several times in order to achieve diagnosticcertainty. Diagnosis at the central and lobar level wastherefore instantaneous, whereas evaluation of all seg-mental arteries took 5–20 min per patient.

All 9 cases of non-diagnostic MRA were caused bypatient motion and breathing artifacts. Bolus timing wascorrect in all examinations since all MRA showed suffi-cient PA enhancement that was rarely associated withpulmonary vein enhancement. Evaluation of coronal rawimages and postprocessing of MIP and MPR imagestook 5–10 min.

Table 1 shows the distribution of diagnostic qualitywith both imaging techniques for the regions evaluated.The MRA showed a percentage of diagnostic qualityranging from 77% (30 of 39) for all examinations to 70%at the segmental level, whereas the percentage of diag-nostic quality in RT-MRI decreased slightly from 100%at the examination level to 96% at the segmental level.Patients with non-diagnostic MRA (n=9) were excludedfrom further evaluation.

The percentage of RT-MRI and MRA examinationswith diagnostic quality at different clinical stages of sus-pected PE is shown in Table 2. All 39 RT-MRI examina-tions reached diagnostic quality including all 5 patients

in stage III. Diagnostic quality of MRA, on the otherhand, depended on patient co-operation: severe dyspneaappeared to impede diagnostic quality in MRA since64.4% (7 of 11) of the MRA examinations in stage II andno MRA examination in stage III reached diagnosticquality. These differences were significant (p<0.05).

Pulmonary embolism

Figure 1 demonstrates PE as depicted by both imagingtechniques in coronal views. Both sequences depicted allemboli. Figure 2 shows PE in a patient with severe dys-pnea which led to respiratory artifacts and marked mo-tion blurring in the MRA sequence, whereas image qual-ity of real-time sequences was not affected by breathingartifacts. Figure 3 shows typical examples of PE presen-tation in RT sequences.

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Table 1 Diagnostic quality of real-time MRI (RT-MRI) and con-trast-enhanced MR angiography (CE-MRA) at different levels

Diagnostic quality Diagnostic qualityof RT sequences of MRA sequences

Examination 39 of 39 (100.0) 30 of 39 (77)Lobar artery 231 of 233 (99) 177 of 233 (76)Segmental artery 668 of 699a (96) 491 of 699 (70)a

Numbers in parentheses are percentagesa Thirty-six of 735 pulmonary segments were not evaluated due toatelectasis (pleural effusion or other compression)

Table 2 Diagnostic quality of RT-MRI and CE-MRA in differentclinical stages of suspected pulmonary embolism

Diagnostic quality Diagnostic qualityof RT examinations of MRA examinations

Stage Ia 23 of 23 (100) 23 of 23 (100)Stage IIb 11 of 11 (100) 7 of 11 (64)Stage IIIc 5 of 5 (100) 0 of 5 (0)Total 39 of 39 (100) 30 of 39 (77)

Numbers in parentheses are percentagesa Asymptomatic or mild dyspneab Severe dyspnea and agitationc Severe dyspnea and decreased blood pressure

Fig. 1a, b A 79-year-old woman. a Contrast-enhanced MRA dataset, b real-time TrueFISP data set in corresponding coronal views

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The MRA and RT-MRI were both capable of depictingembolic material adherent to the vessel wall as well as freefloating thrombi. In 30 patients undergoing diagnostic ex-aminations with both techniques, 60 main PA, 177 lobar,and 491 segmental arteries were evaluated; 1 patient hadundergone a previous resection of the right lower lobe.

Frequency of PE varied with clinical stage. In MRA,9 of 23 (39%) patients in stage I and 4 of 7 patients(57%) in stage II had PE. As MRA was not diagnostic inany stage-III examination and in 37% of stage-II exam-inations (Table 2), direct thrombus visualization in RT-MRI was used as “prima facie evidence” in the fol-lowing examinations: 4 of 5 patients (80%) at clinicalstage III and 7 of 11 patients (64%) in stage II had visi-ble thrombotic material and, therefore, PE. Of nine non-diagnostic MRA examinations, six had PE in RT-MRI.Two patients received systemic lysis using rTPA as aconsequence of the MR examination.

Table 3 depicts the frequency of PE at different ana-tomical levels as well as sensitivity, specificity, and posi-tive/negative predictive values for RT-MRI. Sensitivity

per examination was 93 and 96% at the lobar level and97% at the segmental level, and specificity was 100% forall three levels. In RT-MRI four false-negative segmentalemboli and two false-negative lobar arteries in two ex-aminations led to one false-negative examination. TheMRA showed clear evidence of thrombotic material intwo middle lobe (ML) arteries as well as in the arteriesof segments 4 and 5, and RT sequences did not depictthrombotic material in either case. Final diagnosischanged in 1 patient with solitary embolism in the ML,whereas the other patient had massive PE with a largeamount of thrombotic material in two lobar PAs.

Table 4 shows the occurrence of PE and the distribu-tion of thrombotic material per examination, and at thecentral pulmonary, lobar, and segmental artery level.Since most patients with PE had more than one affectedpulmonary segment, with one segment sufficing for thediagnosis of PE, the frequency of PE increased from26% of segmental PA and 27% of lobar PA to 47% of allexaminations. Quantitative measurements (SNR, SI ra-tio, and CNR) of representative embolic material are

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Fig. 2a–d A 77-year-old woman. a Contrast-enhancedMRA data set and b real-timeTrueFISP data set in corre-sponding coronal views.c Transversal and d sagittalreal-time data

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Fig. 3a–d Spectrum of appear-ance of pulmonary embolism in real-time TrueFISP imagesin a 62-year-old woman

Table 3 Frequency of pulmonary embolism and diagnostic reliability of RT-MRI at different levels. PPV positive predictive value, NPVnegative predictive value

Per examination Main pulmonary artery Lobar artery Segmental artery

MRA 14 of 30 (47) 5 of 60 (8) 48 of 177 (27) 126 of 491 (26)RT 13 of 30 (43) 5 of 60 (8) 46 of 177 (26) 122 of 491 (25)

Subgroup: examinations with non-diagnostic MRA only (n=9), direct thrombus visualization in RT-MRIRT 6 of 9 (67) 5 of 18 (28) 10 of 54 (19) 33 of 177 (19)

Sensitivity and specificity of RT-MRI

Number Sensitivity Specificity PPV NPV

Examinations 30 13 of 14 (93) 16 of 16 (100) 13 of 14 (93) 16 of 17 (94)Lobar arteries 185 46 of 48 (96) 137 of 137 (100) 46 of 46 (100) 137 of 139 (99)Segmental arteries 491 122 of 126 (97) 402 of 402 (100) 122 of 122 (100) 365 of 369 (99)

Numbers in parentheses are percentagesRT-MRI missed the diagnosis of PE in four segments and two lobar arteries leading to one false-negative examination

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given as means±SD. The SNR of blood was 18.1±6.7.For central pulmonary arteries SNR of embolic material(n=5) was 5.7±2.1, the SI ratio blood/embolic materialamounted to 4.3±1.7, and the CNR was 11.9±4.1. For lobar emboli (n=18) the values were as follows: SNR8.7±4.7; SI ratio 3.2±0.6; and CNR 10.2±3.2. The re-spective values for segmental emboli (n=22) were as fol-lows: SNR 5.2±2.3; SI ratio 6.6±3.2; and CNR 13.5±3.4.

Nuclear medicine

Seventeen perfusion scintigraphies were available in pa-tients with clinical stage-I PE. All MRA and RT-MRI ex-aminations reached diagnostic quality in this subgroup.Scintigraphy was positive for acute PE in 6 of 17 pa-tients (35%), and RT-MRI was positive in 5 of these 6patients (5 of 17, 29%). Sensitivity, specificity, PPV, andNPV for RT-MRI, therefore, were 83% (5 of 6), 100%(11 of 11), 100% (5 of 5), and 92% (11 of 12), respec-tively. The MRA depicted all 6 patients with PE correct-ly; thus, sensitivity, specificity, PPV, and NPV was 100%for MRA in this subgroup.

Coincidental findings

Coincidental findings included three pleural bleedings,three gastric herniations, segmental and lobar atelectasisin 5 patients, vertebral hemangioma in 1 patient, andrupture of an ascending aortic graft in 1 patient. All thesefindings were detected by RT-MRI alone, and no further

sequences (e.g., T1-weighted spin-echo sequences) wererequired to establish the diagnosis. Apart from the aorticgraft rupture, when MRA was performed to present find-ings in a way clinicians are more familiar with, all othercoincidental findings would have been overlooked byMRA.

Discussion

The RT-MRI with TrueFISP sequences was used for diagnosis of PE for the first time. Diagnosis of centraland lobar PE was immediate and diagnosis of segmentalPE was reliable. Patients in this study presented more se-vere stages of PE, which led to a high rate of inconclu-sive MRA examinations. Among these severely ill pa-tients in particular, reliable performance of RT-MRI ide-ally complemented MRA and allowed emergency diag-nosis and fast therapeutic decisions.

Presently, however, CTA is the most commonly usedimaging modality for diagnosing PE [6]. Sensitivity ofCTA reaches up to 94% for segmental PE [16] but dependson vessel size [17]. Combined assessment of PE and pe-ripheral thrombosis is feasible [18]; however, radiation ex-posure and the necessity to administer iodinated contrastmedia are disadvantages of CTA. The MRA does not sharethese disadvantages and has been repeatedly evaluated forPE diagnosis. Sensitivity is comparable to single-sliceCTA [10, 11, 19] and was even slightly superior in autopticcontrolled porcine studies [20, 21], ranging from 60 [22]and 85% [19] to 100% [10]. This evolving role of MRAjustified its use as a reference method in the present study;

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Table 4 Distribution of em-bolic material in the left andright pulmonary arteries and at the lobar and segmental level diagnosed with MRA.RUL right upper lobe, ML middle lobe, RLL rightlower lobe, LUL left upperlobe, LLL left lower lobe

Frequency of pulmonary embolism in the left and right pulmonary arteries and at the lobar level

Right pulmonary artery 3 of 30 (10) Left pulmonary artery 2 of 30 (7)RUL 9 of 30 (30) LUL 6 of 30 (20)ML 10(8) of 29 (35) Lingula 5 of 29 (17)RLL 11 of 29 (38) LLL 7 of 30 (23)Total right 30 of 88 (34) Total left 18 of 89 (20)Lobar arteries 48 of 177 (27)

Frequency of pulmonary embolism at the segmental level

S2 8 of 27 (30) S2 5 of 28 (18)S3 11 of 27 (41) S3 8 of 27 (30)S4 9(7) of 26 (35) S4 6 of 27 (22)S5 8(6) of 27 (30) S5 6 of 26 (23)S6 5 of 27 (19) S6 3 of 27 (11)S7 4 of 23 (17) – –S8 8 of 24 (33) S8 3 of 25 (12)S9 9 of 25 (36) S9 11 of 23 (48)S10 7 of 24 (29) S10 15 of 23 (65)Total right 77 of 259 (30) Total left 49 of 232 (21)Segmental arteries 126 of 491 (26)

Differences for RT-MRI are shown in parenthesesDiffering values for RT-MRI are shown in italic letters

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however, long periods of apnea necessary for CE-MRAlimit its indication to non-emergency examinations.

Unlike MRA, RT imaging is not, by definition, sus-ceptible to motion artifacts. Due to the non-segmentedacquisition of the image, motion artifacts occur only dur-ing the acquisition of each individual image (0.4–0.5 sfor the TrueFISP sequence applied); thus, TrueFISP se-quences are suitable for fast whole-body [23] and emer-gency imaging [15]. In addition to this robustness, True-FISP’s inherent T2 contrast led to a CNR (embo-lus/blood) sufficient to depict PE without use of contrastagent, thereby reducing preparation time and error sourc-es in urgent diagnostics.

All 39 RT-MRI examinations reached diagnostic qualityregardless of clinical stage or respiratory motion even in pa-tients with massive PE. Preceding volunteer examinationsshowed robust RT image quality for breath rates up to30 breaths/min, and artifacts increased markedly at >40breaths/min. The amount of embolic material, however, in-fluenced the diagnostic certainty: central and lobar PE wasdiagnosed immediately, whereas isolated segmental PE re-quired meticulous analysis. Systolic blood flow caused in-flow artifacts in the main PA on several images, but usuallythis area was artifact free on directly preceding or followingimages, and diagnostic confidence was not affected. Due to31 non-diagnostic (mainly middle lobe) segmental arteriesin RT-MRI, two segmental PE were missed and 1 patient inclinical stage I was therefore classified as a false negative.As patients with massive dyspnea had advanced stages ofPE, the diagnostic performance (sensitivity 93%) was suffi-cient for immediate diagnosis in an emergency setting. Af-ter a learning curve in image interpretation, the number of320 RT images assuring the depiction of every segmentalPA in three planes on several images could be markedly re-duced to achieve an acquisition time of 1 min.

The MRA showed the following complementary char-acteristics: the diagnostic performance of MRA did notdepend on the location, but on the amount of embolic ma-terial, i.e., the clinical condition of patients. The MRAprovided reliable results, particularly in (mostly non-dys-pneic) patients with a smaller embolic burden, where di-agnostic confidence was better than it was with RT-MRI.

The PE prevalence of 47% in our study was marked-ly higher than previously reported (35% diagnosed by pulmonary angiography [4]: 19.6–44% found by CTA [5, 24, 25] and 26.6–36% for MRA [10, 11, 19], whilethe distribution of emboli (predominantly right and mul-tiple; Table 4) paralleled autoptic findings [26]. Part ofthe high prevalence is credited to the clinical judgmentof the referring cardiologists (complemented by ECG,D-dimer, echocardiography and duplex sonography).More importantly, the previously very limited availabili-ty of MR as the sole imaging modality (no CT, day-timeavailability of scintigraphy), and the initiation of RT-MRI as an emergency approach, resulted in initial self-restriction. Patients were probably referred after a more

specific clinical selection, augmenting the pretest proba-bility.

This higher proportion of advanced clinical stages of PEand of dyspneic patients explains the considerably highernumber of non-diagnostic MRA examinations (23%). Theclinical condition of patients, however, is seldom stated inpublished studies, but has to be deduced from the rate ofnon-diagnostic examinations or positive findings. Non-di-agnostic quality is reported for MRA in 4–15% [10, 11,27], for pulmonary angiography in 3% [4, 28], and forCTA in 2.7–10.4%, depending on technique [24, 29]. Shal-low breathing degrades the quality of single-slice CTA on-ly slightly [5, 30] but hinders subsegmental PA evaluationmore substantially [24]. Considering the prevalence of PEamong dyspneic patients, the robustness of our MRA maybe within the reported range. Artificial ventilation did nothamper RT-MRI, but this applies to breath-hold CE-MRAor CTA examinations also, as image acquisition can be ac-quired in breath-hold position in these patients.

Several approaches to overcome long breath-holdingperiods for CE-MRA have been proposed: high-power gra-dients allow the acquisition time to be limited to 4 s [31];however, for ultrafast acquisition, temporal resolution hasto be traded for spatial resolution. In our experience withthis approach dyspnea is unproblematic, but lower spatialresolution makes unambiguous evaluation of all segmentalPA difficult. Parenchymal perfusion may be accessible thisway [32] since the limited spatial resolution averages oth-erwise undetectable (sub)subsegmental vasculature. Navi-gator-echo sequences allowed free breathing, but an acqui-sition time of up to 16 min required non-approved intra-vascular contrast agents [33]. We nevertheless chose a 512-matrix-size MRA for better diagnostic confidence for seg-mental PE, a factor which outweighed the slightly longeracquisition time: motion blurring increased only a littlefrom a matrix size of 256×256 (17 s) to 512×512 (22 s).

As the mentioned coincidental findings indicate, pleu-ral and pericardial fluid collection and aortic dissection oracute rupture could be easily diagnosed by RT-MRI,which is consistent with a study on aortic aneurysm anddissection [13]. Afflictions of the pulmonary parenchyma(bleeding, aspiration, infiltration, and atelectasis) could belocalized and quantified accurately. This advantage overpulmonary angiography, scintigraphy, and CE-MRAmatches the ability of CTA to detect side diagnoses.

A possible algorithm using MRI as a first-line test forPE (wherever symptoms, d-dimer, and/or ECG give riseto suspicion) should start with RT-MRI. The examinationcan be terminated immediately after embolic material ora significant side diagnosis is detected (in dyspneic pa-tients usually after 20–40 s). Patients with negative re-sults after the first RT slab are typically not dyspneic andtolerate the protocol’s continuation to allow increases insensitivity (two more RT-MRI orientations and MRA).Segmental or larger PE is excluded if all RT-MRI andMRA images reveal no PE.

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Further studies need to address the sensitivity of RT-MRI compared with established CTA since theevolving, but still controversial, role of MRA as a refer-ence method, represents the major limitation of the pres-ent study. Only a part of our collective could be exam-ined by perfusion scintigraphy. In our study the accuracyof RT-MRI was comparable to that of established tech-niques, but because of a selection bias, the results are on-ly indicative (lower prevalence of PE in the scintigraphysubgroup and daytime availability of scintigraphy).

Conclusion

Our results demonstrated the feasibility of MRI in astudy population unfavorable for CE-MRA, as well asthe strength of RT-MRI, which proved to be very robust

and reliable for diagnosing PE regardless of the patient’sclinical condition. The RT-MRI required neither venousaccess nor ECG, and predefined protocols with oversizedexamination volumes obviated proper positioning or er-ror-prone parameter adaptation; hence, emergency diag-nostics are feasible within 1–3 min. A combination ofRT-MRI for acute central or lobar PE and differential di-agnosis, and MRA—more vulnerable to motion arti-facts—for reliable diagnosis at the segmental level cov-ers the whole range of clinical presentations of acute PEincluding artificially ventilated patients. The RT-MRI is,therefore, included in our work-up for PE. Future indica-tions for MRI-based diagnosis of PE may no longer berestricted to niche indications (such as contraindicationagainst iodinated contrast media), but may also includeemergency diagnostics.

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