Effects of injection rate and dose on image quality in time-resolved magnetic resonance angiography...

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Eur Radiol (2007) 17: 13941402 DOI 10.1007/s00330-006-0493-x MAGNETIC RESONANCE Harald Kramer Henrik J. Michaely Martin Requardt Martin Rohrer Scott Reeder Maximilian F. Reiser Stefan O. Schoenberg Received: 25 November 2005 Revised: 21 August 2006 Accepted: 28 September 2006 Published online: 18 November 2006 # Springer-Verlag 2006 Effects of injection rate and dose on image quality in time-resolved magnetic resonance angiography (MRA) by using 1.0M contrast agents Abstract In time-resolved MRA (TR MRA), injection parameters and contrast agent (CA) dose are important factors influencing image quality. In this study, three different injection schemes with different CA volumes were evaluated in 12 healthy volun- teers. Injection rates between 0.2 and 0.8 ml/s were evaluated with CA volumes of 10 and 20 ml. To measure circulatory parameters, cine cardiac MRI was performed before each exam. Spatial resolution could be reduced to 2×1.4×2 mm 3 , temporal resolution was 2.25 s/frame. To exclude signal saturation at high CA concentrations, a phantom with fixed CA concentrations was placed in the field of view. SNR was measured, and the area under the curve of the arterial signal of the different injection schemes was calculated. Results showed the largest diagnostic window at a relatively slow injection rate of 0.4 ml/s and a CA volume of 10 ml. Circulatory parameters have an important impact on CA arrival, so delay times have to be set depending on these parameters. Keywords MRA . Time-resolved contrast-enhanced MRA . Injection rate Introduction Catheter-based multi-station digital subtraction angiogra- phy (DSA) is regarded as the gold standard for the eval- uation of vascular disease. However, its invasiveness, cost and morbidity indicate the need for other diagnostic algorithms. Magnetic resonance angiography (MRA) is increasingly used for diagnosis and management of central and peripheral vascular diseases particularly because of the absence of ionizing radiation and nephrotoxic contrast agents (CA) in these often multi-disease vascular patients who frequently suffer from chronic renal insufficiency [1]. Contrast-enhanced (CE) MRA overcame many of the shortcomings of time-of-flight (TOF) angiography but revealed new limitations. In recent years, the limitations of CE MRA, such as reduced spatial resolution, long acqui- sition time and the absence of temporal resolution, have been addressed [2, 3]. The introduction of parallel imaging techniques (PAT) helped increase spatial resolution to values of 1 mm 3 , which is almost comparable to DSA, whereas microvas- cular changes can also be detected by MR perfusion imaging [4]. On the other hand, PAT helped to shorten acquisition times to a tolerable range so that patient motion or breathing artifacts are no longer considered a major drawback. However, the remaining major disadvantage H. Kramer . H. J. Michaely . M. F. Reiser . S. O. Schoenberg Institute of Clinical Radiology, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany M. Requardt Siemens Medical Solutions, Erlangen, Germany M. Rohrer Schering AG, Berlin, Germany S. Reeder Department of Radiology, University of Wisconsin, Madison, WI, USA H. Kramer (*) University Hospital of Munich, Campus Grosshadern, Ludwig Maximilian University, Marchioninistraße 15, 81377 Munich, Germany e-mail: harald.kramer@med. uni-muenchen.de Tel.: +49-89-70953250 Fax: +49-89-70958822

Transcript of Effects of injection rate and dose on image quality in time-resolved magnetic resonance angiography...

Eur Radiol (2007) 17: 1394–1402DOI 10.1007/s00330-006-0493-x MAGNETIC RESONANCE

Harald KramerHenrik J. MichaelyMartin RequardtMartin RohrerScott ReederMaximilian F. ReiserStefan O. Schoenberg

Received: 25 November 2005Revised: 21 August 2006Accepted: 28 September 2006Published online: 18 November 2006# Springer-Verlag 2006

Effects of injection rate and dose on imagequality in time-resolved magnetic resonanceangiography (MRA) by using 1.0M contrastagents

Abstract In time-resolved MRA(TR MRA), injection parameters andcontrast agent (CA) dose are importantfactors influencing image quality. Inthis study, three different injectionschemes with different CA volumeswere evaluated in 12 healthy volun-teers. Injection rates between 0.2 and0.8 ml/s were evaluated with CA

volumes of 10 and 20 ml. To measurecirculatory parameters, cine cardiacMRI was performed before eachexam. Spatial resolution could bereduced to 2×1.4×2 mm3, temporalresolution was 2.25 s/frame. Toexclude signal saturation at high CAconcentrations, a phantom with fixedCA concentrations was placed in thefield of view. SNR was measured, andthe area under the curve of the arterialsignal of the different injectionschemes was calculated. Resultsshowed the largest diagnostic windowat a relatively slow injection rate of0.4 ml/s and a CA volume of 10 ml.Circulatory parameters have animportant impact on CA arrival, sodelay times have to be set dependingon these parameters.

Keywords MRA . Time-resolvedcontrast-enhanced MRA .Injection rate

Introduction

Catheter-based multi-station digital subtraction angiogra-phy (DSA) is regarded as the gold standard for the eval-uation of vascular disease. However, its invasiveness, costand morbidity indicate the need for other diagnosticalgorithms. Magnetic resonance angiography (MRA) isincreasingly used for diagnosis and management of centraland peripheral vascular diseases particularly because of theabsence of ionizing radiation and nephrotoxic contrastagents (CA) in these often multi-disease vascular patientswho frequently suffer from chronic renal insufficiency[1]. Contrast-enhanced (CE) MRA overcame many of the

shortcomings of time-of-flight (TOF) angiography butrevealed new limitations. In recent years, the limitations ofCE MRA, such as reduced spatial resolution, long acqui-sition time and the absence of temporal resolution, havebeen addressed [2, 3].

The introduction of parallel imaging techniques (PAT)helped increase spatial resolution to values of 1 mm3,which is almost comparable to DSA, whereas microvas-cular changes can also be detected by MR perfusionimaging [4]. On the other hand, PAT helped to shortenacquisition times to a tolerable range so that patient motionor breathing artifacts are no longer considered a majordrawback. However, the remaining major disadvantage

H. Kramer . H. J. Michaely .M. F. Reiser . S. O. SchoenbergInstitute of Clinical Radiology,University Hospital of Munich,Ludwig Maximilian Universityof Munich,Munich, Germany

M. RequardtSiemens Medical Solutions,Erlangen, Germany

M. RohrerSchering AG,Berlin, Germany

S. ReederDepartment of Radiology,University of Wisconsin,Madison, WI, USA

H. Kramer (*)University Hospital of Munich,Campus Grosshadern,Ludwig Maximilian University,Marchioninistraße 15,81377 Munich, Germanye-mail: [email protected].: +49-89-70953250Fax: +49-89-70958822

was the absence of dynamic information with the potentialproblem of improper timing when using a fixed delay afterCA administration. This may lead to insufficient arterialfilling or nondiagnostic venous opacification.

The introduction of time-resolved contrast-enhancedMRA (TR-CE-MRA/4D-MRA) was a first step to over-come this limitation as well, even if temporal and spatialresolution were still low [5–8]. The combination of TR-CE-MRA and PAT on a 1.5 T system enabled the acqui-sition of dynamic angiographic information at a temporalresolution of less than 2.5 s/frame with a satisfactory spatialresolution [9].

The drawback of all these modifications is a decrease insignal-to-noise ratio (SNR) in CE-MRA because imageSNR is proportional to the square root of data acquisitiontime and inversely proportional to the voxel size. Con-sequently, low SNR is expected for high spatial resolutionof images acquired with a high frame rate. One approach tosolve this problem is to use a 1M CA rather than the widelyused 0.5M CA [10, 11], which compensates for the PAT-related signal loss. All of these modifications contribute tomaking TR-CE-MRA an appropriate imaging method fordiagnosis of peripheral and central vascular disease. So far,no systematic studies in regard to the dosing and injectionschemes of 1M CA have been performed for TR-CE-MRA.

Thus, the aim of this study was to systematicallyevaluate how to achieve optimum image quality at lowestrequired temporal resolution and CA dose in the peripheralarteries and to relate these findings to influences fromcirculatory parameters [12]. Because imaging of thearteries in the calves represents a particular challenge toCE-MRA, this vascular bed was used as a target area forthe study. To compensate for the well-known loss of SNRwhen applying parallel imaging techniques, 1.0M CAwasused.

Material and methods

The study was approved by the institutional review board(IRB) and oral and written consent was obtained from eachof the volunteers. None of authors who had access tovolunteer-related data were industry employees.

Subjects

Twelve healthy male individuals (28±1.7 years of age,25–31) with no history of cardiac or vascular diseaseeach underwent TR-CE-MRA examinations with threedifferent imaging protocols. Due to restrictions of theinsurance company, only male volunteers were allowed toparticipate in the study. Certainly young healthy volunteersare not representative of patients with vascular diseases.The study was to evaluate different injection schemes and

their impact on image quality. Implementation for use inpatient exams needs further investigation.

Prior to each MRA examination, the circulatory param-eters including heart rate and blood pressure were mea-sured as part of the pre-study physical examination. Resultswere compared with a single sample t-test; significancelevel was set to a value of P=0.05. A minimum delay of7 days between each MR examination was set to excludeany CA contamination from the previous examination. Allvolunteers were free to stop their participation at any time.

Imaging protocol

All volunteers were examined on a 1.5 T eight-channel MRsystem (Magnetom Sonata, Siemens Medical Solutions,Erlangen, Germany). For imaging of myocardial function,a cardiac-gated segmented steady-state free-precessiontechnique (TrueFISP) was used with a temporal resolutionof 48 ms and a slice thickness of 8 mm covering the shortaxis of the heart in 10–12 contiguous slices. Functionalparameters of the left ventricular myocardium, includingend-diastolic volume (EDV), end-systolic volume (ESV)and ejection fraction (EF) normalized to body surface, werecalculated for all individuals in all examinations using adedicated post-processing software (ARGUS, SiemensMedical Solutions). These parameters were identified toexclude the influence of different circulatory circumstanceson image quality, e.g., different CA arrival times.

For TR-CE-MRA measurements, a 12-element surfacecoil with 6 anterior and 6 posterior receiver elements wasused, placed on the knees to cover the superficial femoralarteries, the popliteal arteries and the trifurcation on bothsides. A phantom with defined increasing concentrations ofCA (2, 5, 10, 20 and 50 mmol/L) warmed to 37°C wasplaced in the middle of the field of view. This phantom wasused as a reference to exclude signal saturation at high CAconcentrations in the vessel. Before each examination, an18G venous access was placed in an antecubital vein of theright arm.

Three different MRA protocols characterized by differ-ent CA injection protocols and doses were applied:

– Protocol 1 (“low flow”) consists of 10 ml of 1.0M CA(Gadovist, Schering, Berlin, Germany) injected at aflow rate of 0.2 ml/s followed by a saline flush of25 ml also injected at a flow rate of 0.2 ml/s.

– Protocol 2 (“medium flow”) differs only in the flowrate which is increased to 0.4 ml/s for the CA as wellas for the saline flush. The doses remain the same(10 ml CA, 25 ml saline).

– Protocol 3 (“high flow”) consists of 20 ml of the sameCA injected at a flow rate of 0.8 ml/s again followed bya saline flush of 25 ml at the same flow rate (0.8 ml/s).

We used 1.0M CA because it is well known that SNRdecreases with parallel acquisition techniques (PAT), espe-

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cially in combination with view-sharing techniques such asTREAT and slow injection rates. Precise injection rateswere ensured through the use of a computer-controlledpower injector (Medrad Spectris, Medrad, Indianola, PA,USA). Fixed delay times between start of the CA admin-istration and start of the measurements were used: 100 sfor the low-flow injection scheme, 50 s for the 0.4 ml/smedium-flow injection scheme, and 25 s for the high-flowinjection scheme (Table 1). These delay times were chosenbecause of the long travel times of the CA through theinjection tube (volume 16 ml) at very low flow rates. Werefrained from filling the injection tubing with CA beforethe exam to preclude any contamination with saline or airbubbles.

Immediately after each examination and 30 min later,heart rate and blood pressure of the volunteers weremeasured by physical examination to exclude any CAreactions.

Time-resolved contrast-enhanced magnetic resonanceangiography (TR-CE-MRA) in combinationwith parallel imaging techniques (PAT)

The center of k-space contains contrast information, whilethe peripheral region of k-space contains edge information.If, for example, k-space was divided into three parts A, Band C from the center to the periphery, readout in repetitivemeasurements as in the case of TR-CE-MRAwould updateall parts A, B, C in an equal way: e.g., ABC-ABC-ABC forthree repetitive measurements (Fig. 1). Since the informa-tion in the periphery of k-space changes more slowly thanthe k-space center during the arrival of the contrast agentbolus [13], it is sufficient to sample the center part of k-space more often than the periphery and to share theperipheral parts of k-space between adjacent frames, there-by decreasing the acquisition time considerably [8].

This principle of k-space acquisition known as view-sharing was combined with PATwith an acceleration factorof 2 to further decrease acquisition time, a technique thatis now called TREAT (time-resolved echo-shared angio-graphic technique) (Fig. 2). Additionally, k-space samplingstarts in the center and moves to the periphery in a spiralorder with equidistant steps between each point in k-space[14]. There are other techniques to increase temporal reso-

lution in MRI, e.g. k-t-SENSE and k-t-BLAST [15, 16].Overall, this leads to a shortened acquisition time for eachtime frame, which implies an increase in temporal resolu-tion with almost unchanged spatial resolution. The param-eters of the TREAT sequence used were as follows: TR2.84 ms, TE 1.07 ms, 3 TREAT segments, PAT factor 2,24 reference lines, matrix 2562, bandwidth 490 Hz/pixel,25° flip angle, 360 mm FoVand 2 mm slice thickness. Thisresults in a spatial resolution of 2.0×1.4×2.0 mm3 and atemporal resolution of 2.25 s/3D slab. Each examinationconsisted of 120 consecutive 3D slabs meaning 120 slabslasting 2.5 s resulting in an acquisition time of 5 min.Measurements were started early enough that the initialframes of all examinations showed no CA filling of thevessels.

Image analysis

After the examinations, every dataset was loaded into acommercially available analysis software (MeanCurve,Siemens Medical Solutions, Erlangen, Germany) to mea-sure the SNR. A region of interest (ROI, mean size0.8 cm2) was placed in an arterial segment at the transitionof the superficial femoral artery to the popliteal artery and asecond one directly proximal to the trifurcation. VenousROIs were placed directly next to the arterial ROIs in thepopliteal vein and the femoral vein (Fig. 3). Six more ROIswere placed in the phantom to measure the signal at six

Table 1 Parameters of the three injection protocols

Injectionprotocol

Flowrate(ml/s)

CAvolume(ml)

Saline volume(ml) & flowrate (ml/s)

Delay(s)

Low flow 0.2 10 25/0.2 100Medium flow 0.4 10 25/0.4 50High flow 0.8 20 25/0.8 25

Fig. 1 k-space divided into three parts. Conventional readout is lineby line from the center to the periphery and back to the center again,e.g., A, B, C, A, B, C, etc.

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defined CA concentrations. Mean signal and standarddeviation were recorded. The upslope of SNR in the arterialvessels was measured from zero CA filling to maximumCA concentration in the vessel.

A problem of SNR calculations with PAT is that thenoise is not homogenously distributed throughout theimage and hence cannot be directly measured. Thereare different methods to calculate the noise when usingPAT. One of them was defined by Henkelman et al. [17]which we also applied in our work. According to this, themean signal of the arterial ROI is divided by the signalstandard deviation of an ROI without CA and multiplied bya factor of 0.7033, which is a standard deviation of adefined ROI in the field of view when using a 12-elementcoil. To account for the underestimation of noise thatoccurs when noise is measured from magnitude images,estimates of the noise were corrected as reported byHenkelman et al. To account for the coil geometry used inthe current study, the correction factor of 0.655 proposedby Henkelman et al. for a single-element coil system wasadjusted and corrected for the use of a 12-element coil arraywith sum-of-squares reconstruction (0.7033) [17–19]. Forthe measured arterial and venous SNR curves, the areaunder the curve (AUC) of the maximum arterial contrast,

and 75 and 50% of the maximum arterial contrast werecalculated using a commercially available statistics soft-ware (SPSS 12.0.1) (Fig. 4).

Du et al. could show that the signal curve shows a rapidupslope depending on the shape of the CA bolus, followedby a downslope of signal to one third of the maximumsignal. The signal remains constant at this level for severalminutes [2]. For calculating the AUC, the upslope part ofthe arterial curve from no contrast to maximum contrastwas mirrored and taken as the arterial AUC (AUCamax). Ifonly the AUC from the starting point to the maximum istaken, the part of good arterial filling without disturbingvenous opacification is missed. Also the venous contrastwas measured. If 50% or more of the venous contrast(AUCv50) affected the arterial AUC, this part of the arterialAUC was subtracted (Fig. 5). The diagnostic window forMRA (DWMRA) with excellent arterial contrast withoutdisturbing venous overlay was thus defined as follows:DWMRA=AUCamax−AUCv50. The sizes of the AUC of thedifferent injection protocols were compared and the extentto which they increased with a faster flow rate either due toa more concentrated CA bolus or a larger CA volume wasevaluated.

Fig. 2 a k-space is divided intothree parts. Readout runs notline by line but elliptically. Inaddition, TREAT contains PAT,so only every second line isacquired. bWhen using TREAT,the center of k-space is sampledmore often than the periphery.Peripheral k-space parts arereconstructed from differentframes. k-space parts are readout A, B, C first, then A, B, A,C, A, etc.

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Statistical analysis

All statistical analysis was performed with commerciallyavailable software (SPSS 12.0.1). To evaluate the sig-nificance of differences in circulatory parameters in termsof blood pressure, ejection fraction and end-diastolic/end-systolic volume, a single sample t-test was used, andsignificance level was set to a value of P=0.05.

Results

Measurement of circulatory parameters showed no signif-icant differences in healthy volunteers; all parametersranged within normal limits (Table 2) [20]. No adverseevents occurred, none of the volunteers were excludedfrom the study, and no CA contamination due to previousexams occurred. No significant differences in CA inflowdepending on the parameters could be detected (P>0.05).

Fig. 3 For measurement of CA inflow and measurement of SNR values, a ROI is placed in an arterial and a venous vessel. Curves ofarterial and venous CA inflow are displayed over time (right image)

Fig. 4 Maximum arterial signalof the different injectionschemes (diamonds0.2 ml/s,10 ml CA; squares 0.4 ml/s,10 ml CA; triangles 0.8 ml/s,20 ml CA) with consistent scal-ing of y-axis

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In none of the 36 exams did the first two frames showarterial contrast enhancement.

In the first injection scheme (10 ml 1.0M CA at a flowrate of 0.2 ml/s), a maximum arterial SNR of 23.1±11.2could be reached in slab number 22 of 120 (55 s after startof measurement) on average. The medium-flow injectionscheme (10 ml CA at a flow rate of 0.4 ml/s) showed amaximum arterial SNR of 40.2±18.2 in slab number 21 of120 (52.5 s after start of measurement) on average.Maximum arterial SNR for the third, high-flow injectionscheme (20 ml CA at a flow rate of 0.8 ml/s) was 84.5±29.8 in slab number 20 of 120 (50 s after start of mea-surement) on average. Signal saturation because of highCA concentration could be excluded by measurement ofthe SNR in the phantom (Fig. 6).

The AUC of the low-flow injection scheme was 395.8,of the medium-flow injection scheme 902.7, and of thehigh-flow injection scheme 1,361.8 (Table 3). The AUCincreased from the low-flow scheme to the medium-flowscheme by the factor of 2.3 but from the medium-flowscheme to the high-flow scheme only by the factor of 1.5.Nearly the same factors were found if the AUC of only75% (AUCa75) or 50% (AUCa50) of the maximum arterialSNR was used.

For determination of the diagnostic window (DWMRA),the values were 137.4 for the slow-flow injection scheme,378.8 for the medium-flow scheme and only 370.1 for thehigh-flow injection scheme. Therefore, the medium-flowprotocol provided the largest and best diagnostic window.The slowest injection rate did not reach sufficient maxi-mum SNR to deliver good diagnostic arterial CA filling.

Fig. 5a, b Time-resolved contrast-enhanced MRA of a healthyvolunteer with three different injection schemes (0.2 ml/s flow rate,10 ml CA; 0.4 ml/s flow rate, 10 ml CA; 0.8 ml/s flow rate, 20 mlCA) at different time points. a “Low-flow” injection scheme with avery slow CA inflow and medium contrast but a long time without

venous overlay. b “Medium-flow” injection scheme with goodarterial contrast and a long period without disturbing veins. c “High-flow” injection scheme with only a little visual increase in contrastbut rapid occurrence of venous overlay

Table 2 Circulatory parameters of the volunteers

SV (ml/min/m2) HR (per min) RR sys (mmHg) RR dias (mmHg) EDV/BSA (ml/m2) EF (%)

37.8±8 67±8 130±8 85±5 75.01±14.8 62.37±2.7

SV Stroke volume, HR heart rate, RR sys systolic blood pressure, RR dias diastolic blood pressure, EDV/BSA end diastolic volumenormalized to body surface area, EF ejection fraction

All parameters were within normal limits

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The highest injection rate provided an overly rapid up- anddownslope, the wash-in curve was too narrow, and thevenous enhancement rose too quickly.

Discussion

Recent developments in MRI and especially in MRA, suchas the implementation of PAT and special sequences fordynamic, time-resolved imaging like TREAT, have shiftedthe focus of diagnostic angiographic imaging from DSA toless invasive MRA. With PAT, the spatial resolution inMRA could be greatly increased and submillimeter iso-tropic resolution in defined anatomic regions could be

obtained. In contrast to DSA, however, MRA could notprovide dynamic information concerning the in- andoutflow of CA. Doppler ultrasound also allows flow withinthe vessels to be assessed but can not be employed in allanatomic areas.

For therapy planning, the dynamic information com-bined with high spatial resolution as provided by DSAis indispensable. These facts not only count when eval-uating the degree of stenosis in patients with renovascularhypertension [21] but also when dealing with peripheralarteries. Details regarding the degree of stenosis orocclusion, rapid or delayed CA inflow and antegrade orretrograde vessel filling are extremely important diagnosticinformation and have to be provided. As mentioned above,this was only possible with DSA until the implementationof time-resolved contrast-enhanced MRA (TR-CE-MRA).Moreover, information about the very distal vessels is ofessence. To get this information, new techniques with analternated acquisition orientation are evaluated [21]. TodayTR-CE-MRA still has a reduced spatial resolution com-pared to high spatial resolution MRA, but both temporaland spatial resolution have achieved a level that featuresdiagnostic accuracy and sometimes can even depict smallvessels in the distal calves or feet that were judged asoccluded in the DSA exam [22, 23].

Various authors have described CA injection protocolswhich were identical to those suitable for high-spatial-resolution MRA, whereas others made attempts to modifyCA injection in order to optimize the parameters for thedynamic MRAmethod to increase image quality [12]. Witheach of the described injection schemes, it is possible to getone good frame. This is even easier with a more circum-scribed CA bolus at higher injection rates.

When dealing with time-resolved MRA, several frameswith a sufficient SNR are desired. It has been hypothesizedthat reducing the injection rate results in an elongation ofthe bolus but also in reduction of intravascular signal. TheAUC of SNR in arterial and venous vessels represents agood estimate of the diagnostic quality of an MRA exam.The optimum curve for several diagnostic questions maybe different. When quantitative assessment of a stenosisis required, a fast upslope of a circumscribed CA bolus isrequired in order to demonstrate the residual lumen of ahemodynamically significant stenosis and to differentiatebetween occlusion with retrograde filling from collateralsversus a pseudo-occlusion.

In other vascular disease entities, a slow inflow of CAmay be favorable, e.g., in the assessment of inflammatorychanges in soft tissue, critical ischemia of the lower limb orarterial-venous malformations. This curve and the AUCdepend upon several factors. The circulatory parametersdefinitely play an important role [24, 25]. Even thoughcirculatory parameters did not differ significantly in ourpopulation of healthy volunteers, we could see the in-fluences of circulatory parameters, e.g., different arrivaltimes of CA in volunteers with high blood pressure and

Table 3 Results of the three injection protocols

0.2 ml/s,10 ml

0.4 ml/s,10 ml

0.8 ml/s,20 ml

Max SNR 20.82 40.18 84.50Slab numbera 21 20 20AUC SNRamax 395.84 902.70 1,361.76AUC SNRa75 349.68 769.12 1,191.42AUC SNRa50 263.60 564.14 901.12aAverage slab number in which the maximum SNR was reachedMax SNR Maximum arterial signal-to-noise ratio, AUC SNRamaxarea under the curve for the max SNR, AUC SNRa75 area underthe curve for 75% of the max SNR, AUC SNRa50 area underthe curve for 50% of the max SNR

0

50

100

150

200

250

300

350

2 mmol/L 5 mmol/L 10 mmol/L 20 mmol/l 50 mmol/L

A.U.

Fig. 6 Signal enhancement determined for five vials filled withCA solutions of different concentrations in serum tempered to37°C. Data determined from TREAT images are plotted versus thecorresponding CA concentration. A linear signal increase can beestablished up to a CA concentration of 10mmol/L and a signalintensity of approximately 250 arbitrary units. For higher CAconcentrations, the curve shows a saturation

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high cardiac output compared to those with lower bloodpressure and lower cardiac output. In addition, parametersof CA application can strongly influence the inflow curve.

The role of injection rate in first-pass signal intensity canbe approximated from the relationship between intra-arterial gadolinium concentration (IA[Gd]), injection rate(IR), cardiac output (CO) and the injected CA concentra-tion ([Gd]Inj): IA[Gd]=(IR/CO)* [Gd]Inj. [12]. Using thisequation, the IA[Gd] for the injection rates used in our study(0.2 ml/s, 0.4 ml/s, 0.8 ml/s) is four-fold higher at 0.8 ml/sthan at 0.2 ml/s or two-fold higher at 0.4 ml/s than at0.2 ml/s. This equation also shows the value of high con-centration CA compared to standard concentration (0.5M).

In our study we used three different injection schemes,all with very slow flow rates compared to standard in-jection rates. In the slowest injection rate scheme, a slowrise in signal with a lower peak intensity, but also a slowdecline and a very slow rise in venous signal was present.There was an arterial signal without any venous signal overa long period, which can be described as a low maximumarterial signal (aSmax) but a large DWMRA. This injectionscheme may be interesting for assessment of soft-tissueperfusion in inflammatory changes such as diabeticpatients with chronic inflammatory changes in their lowerextremities [23].

Conversely, the fastest injection scheme of 0.8 ml/sresulted in an abrupt rise in signal with higher peak signalintensity and an abrupt decrease as well as a rapid venoussignal increase. Therefore, the time period of arterial signalwithout venous overlay was short. A fast signal increasewith a great maximum is advantageous to accurately assessthe degree of a high-grade stenosis and to differentiatebetween a pseudo-occlusion and an occlusion with distalretrograde vessel filling from collateral vessels. A typicalimplementation for this type of CA application is high-spatial-resolution MRA of the carotid artery with ellipticalcentric scanning and submillimeter voxel sizes in whichan initial sharp rise in CA is required for acquisition ofthe central k-space followed by periphery during venousreturn [26].

In cases where good temporal resolution is neededwithout high spatial resolution, our study showed that aninjection rate of only 0.4 ml/s and a volume of only 10 mlprovided the best diagnostic window with high peakarterial signal and a large period of arterial CA fillingwithout venous overlay. Certainly the AUC increaseswith faster injection schemes because of the more circum-scribed CA bolus and consequently a higher SNR, but itdoes not increase proportionally with higher flow rates orCA volumes. Saturation effects are unlikely because thepeak arterial signal intensity remained below the level atwhich saturation effects were observed in the phantommeasurements.

The area under the curve of 50–100% of the maximumarterial signal minus more than 50% of the venous signal

(DWMRA=AUCa50–100−(AUCv100−AUCv50)) represents agood diagnostic window with good arterial filling and nobothersome venous overlay. Such an AUC was mainlyfound for the medium-flow injection scheme. Although theAUC rises with higher injection rates because of the highermaximum arterial signal, it does not increase proportion-ally, and it decreases again if the injection rate is too highbecause of a narrow peak and abrupt rise in the venoussignal. The highest injection rate showed up- and down-slopes that were too rapid, the available imaging windowwas too narrow, and venous filling rose too quickly.

Compared to high-spatial-resolution MRA, time-re-solved MRA showed a decrease in SNR because of shorteracquisition times and the application of PAT. This problemwas well known previously, and the application of 1.0MCA compared to the normally used 0.5M CA helpedimprove SNR again [27]. Compared to DSA, the demandfor temporal resolution can be met, although spatial reso-lution may be limited.

In conclusion, there is still a trade-off between spatialand temporal resolution in TR-CE-MRA. However, ourstudy demonstrated the feasibility of achieving sufficienttemporal resolution in peripheral MRA by application ofoptimized k-space sampling techniques, appropriate injec-tion protocols and a high-concentration MRI CA. Evenwith the optimum examination technique, time-resolvedMRA has limitations in spatial resolution and must becombined with an additional high-spatial-resolution study.Preliminary results indicate that the combination of theTREAT sequence with a 3.0T MR system allows for aremarkable increase both in spatial and temporal resolution[28].

Conclusion

Due to the implementation of PAT and special sequencesfor dynamic MRA, such as TREAT, time-resolved MRAcan be obtained. Depending on circulatory parameters,10–20 ml of CA are adequate for good image quality with arelatively high SNR in the arterial phase without venousoverlay. The decrease in SNR because of the implementa-tion of parallel imaging techniques can be absorbed by ahigh-concentration CA such as a 1.0M CA. Increase in theAUC is not proportional to CA volume and injection ratedespite the absence of saturation effects. A 10-ml volumeof CA at a flow rate of 0.4 ml/s showed the best diagnosticresults with a good arterial signal without disturbingvenous overlay. Compared to exclusively diagnostic DSA,dynamic MRA now has as its only restriction limitedspatial resolution. This problem can be solved with acombined exam consisting of time-resolved MRA andhigh-spatial-resolution MRA.

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