Original Research

High Temporal Resolution SSFP Cine MRI forEstimation of Left Ventricular Diastolic Parameters

Ramkumar Krishnamurthy, MS,1 Amol Pednekar, PhD,2 Benjamin Cheong, MD,3

and Raja Muthupillai, PhD3*

Purpose: To obtain high temporal resolution (HTR) mag-netic resonance (MR) steady-state free-precession (SSFP)cine cardiac images by using multichannel radiofrequency(RF) hardware and parallel imaging techniques; to studythe effect of temporal resolution; and to compare thederived left ventricular (LV) diastolic filling parameterswith echocardiographic results.

Materials and Methods: HTR images were acquired in 13healthy volunteers using a 1.5 T scanner with 32 RFchannels and sensitivity encoding (SENSE) and k-t broad-use linear-acquisition speedup technique (k-t BLAST)imaging techniques. LV diastolic parameters were calcu-lated and compared to conventional echocardiographicindices such as the isovolumic relaxation time (IVRT) andE/A ratio. The need for HTR was assessed and the MRresults were compared with echocardiographic results.

Results: The HTR (�6-ms) images yielded higher peak fill-ing rates, peak ejection rates, and peak atrial filling rates.A progressive decline in filling and ejection rates wasobserved with worsening temporal resolution. The IVRTsand E/A ratios measured with MR versus echocardiogra-phy were in broad agreement. Also, SENSE and k-tBLAST yielded similar diastolic functional parameters.

Conclusion: With SENSE or k-t BLAST and modern hard-ware, HTR cine images can be obtained. The lower tempo-ral resolutions (30–50 ms) used in clinical practice reduceLV filling rates by �30% and may hinder characterizationof transient phenomena such as the IVRT.

Key Words: magnetic resonance imaging; high temporalresolution; SSFP; k-t BLAST; left ventricle; filling rates,left ventricular; echocardiographyJ. Magn. Reson. Imaging 2010;31:872–880.VC 2010 Wiley-Liss, Inc.

LEFT VENTRICULAR (LV) diastolic dysfunction is animportant early indicator of many diseases, includingcoronary artery disease, congestive heart failure, hy-pertrophic cardiomyopathy, valvular heart disease, di-abetes mellitus, and hypertension (1–6). Because ofits widespread availability and high temporal resolu-tion, echocardiography is the method of choice forassessing LV function (7,8). Various echocardio-graphic parameters are available, eg, E wave (rapidearly diastolic filling); A wave (late diastolic filling dueto atrial contraction), and the isovolumic relaxationtime (IVRT, the earliest phase of diastole from aorticvalve closure to mitral valve opening), to name a few.These indices vary with different stages of diastolicdysfunction and are well described in the seminal ar-ticle by Garcia et al (7). An LV volume curve that hasbeen sufficiently sampled over the duration of the car-diac cycle (time–volume curve) can provide valuableinsight into the performance of the cardiovascularpump (9). The accurate evaluation of diastolic func-tion is important, as diastolic dysfunction can lead tosignificant morbidity and mortality (10).

Magnetic resonance imaging (MRI) is increasinglypreferred for imaging many cardiovascular pathologicconditions (11,12). Several studies have shown thatcardiovascular MR can be used to measure LV vol-umes, systolic function, and mass with excellent ac-curacy and reproducibility (13–15). The temporal re-solution of 30–50 ms that is routinely used inconventional ‘‘cine’’ cardiac MR images is sufficient todetermine the end-systolic volume (ESV) and end-dia-stolic volume (EDV) and, therefore, to calculate the LVejection fraction. However, it is unclear whether thisresolution is sufficient to completely characterize vari-ous other physiologically relevant events within theentire cardiac cycle. For example, many physiologicphenomena within the cardiac cycle, such as theIVRT, are of the same order as this temporal resolu-tion. In fact, despite its superior soft-tissue contrast,MRI has a relatively modest temporal resolution; thisis one of the reasons why echocardiography is cur-rently the preferred method for investigating diastolicfunctional indices.

Recent advances in MRI methodologies that exploitspatial coil sensitivity variations (sensitivity encoding[SENSE]) and spatiotemporal correlations (the k-t

1Department of Bioengineering, Rice University, Houston, Texas, USA.2Philips Medical System, Cleveland, Ohio, USA.3The Department of Radiology, St. Luke’s Episcopal Hospital, Houston,Texas, USA.

*Address reprint requests to: R.M., 6720 Bertner Ave., MC 2-270,Houston, TX 77030. E-mail: RMuthupillai@sleh.com

Received September 2, 2009; Accepted January 8, 2010.

DOI 10.1002/jmri.22123Published online in Wiley InterScience (www.interscience.wiley.com).

JOURNAL OF MAGNETIC RESONANCE IMAGING 31:872–880 (2010)

VC 2010 Wiley-Liss, Inc. 872

broad-use linear-acquisition speedup technique [k-tBLAST]), as well as improvements in MRI hardware(multichannel radiofrequency [RF] coil systems), havemade it possible to acquire cardiac cine MR imagesvery rapidly (16–18). This ability has been exploited toreduce the image-acquisition time, increase the spa-tial resolution, or increase coverage within the limitsof a single patient breath-hold (19,20).

We hypothesized that by using a 32-channel RF sys-tem in conjunction with parallel imaging techniques,we could develop a cardiac cine MRI method that couldprovide a temporal resolution sufficient to estimatemany transient phenomena involving diastolic func-tional indices. The primary purpose of this prospectivestudy was to test our hypothesis in volunteers and toevaluate the potential for clinical application of hightemporal resolution (HTR) cine imaging in estimating di-astolic functional indices such as the IVRT.

In this article we describe 1) data-acquisition meth-ods for obtaining cardiac cine MR images with a hightemporal resolution (�6 ms); 2) image-processingalgorithms for segmenting the LV cavity in the result-ing images so as to derive indices that characterize di-astolic function; 3) the effect of temporal resolution onthe parameters; and 4) the results of MR-derived dia-stolic functional indices versus the results ofechocardiography.

MATERIALS AND METHODS

Patient Population

The patient population for the cine-SSFP (steady-statefree-precession) studies comprised 33 asymptomatic vol-unteers (24 men, 9 women) with a mean age of 36 6 9years. The study was approved by the InstitutionalEthics Committee and complied with the Health Insur-ance Portability and Accountability Act of 1996. All sub-jects gave written informed consent before being enrolledin the study. The study population was divided into twogroups to facilitate the testing of our hypotheses.

In the first group of 20 subjects (12 men and 8women; average age, 38 6 9 years; mean ejectionfraction, 58.1 6 5.2), and the cardiac cine MR imagesobtained in this group of volunteers was used to vali-date the image processing algorithms used in thestudy. In particular, the LV volumes computed byusing the semiautomated image-processing algorithmand the modified Simpson algorithm to estimate thetotal LV volume from three short-axis slices were vali-dated against the LV volumes computed by using anexpert’s manual LV contours.

In the remaining 13/33 subjects (12 men and 1woman; average age, 28 6 6 years), HTR cine MRimages were acquired. The modified Simpson’s algo-rithm validated in the first group of 20 subjects wasapplied to calculate the diastolic parameters from thethree cine-SSFP short-axis slices acquired at HTR.

Image Acquisition

All imaging was done with a 1.5 T commercial scan-ner (Achieva, Philips Medical Systems, Best, The

Netherlands) equipped with a 32-channel RF systemand vector-cardiographic (VCG) gating. A 32-elementphased-array surface coil was used for MR signalreception. In 3/13 patients the 32-element coil wasnot available and a 16-element phased array surfacecoil was used instead. The 32-channel coil has twosets of 16 coil elements (4 rows * 4 columns) distrib-uted in the anterior and posterior sections of the coil.The outside coil dimensions were 30 cm (LR direction)and 25 cm in the FH direction. The signal picked upfrom each coil element was independently processedby a receiver chain before image reconstruction. TheMRI protocols used for data acquisition (both modifiedSimpson algorithm validation and HTR imaging) aredescribed below.

In all 33 volunteers, scout images of the thoraciccavity were obtained along three orthogonal planeswith a non-VCG–gated SSFP technique. With thesesingle-phase scout scans, a series of VCG-gated cine-SSFP images were acquired during suspended respi-ration in the following order: a two-chamber view, afour-chamber view, and a series of contiguous short-axis slices (8–12 slices) covering the entire LV fromthe apex to the base (the level of the mitral valveannulus). The imaging parameters used for the con-ventional temporal resolution of 40–50 ms were as fol-lows: TR/TE/flip angle ¼ 3.0–3.2 ms/1.5–1.6 ms/55�;acquired voxel size ¼ 2 � 2 � 8 mm3; reconstructedvoxel size ¼ 1.76 � 1.76 � 8 mm3; SENSE accelera-tion factor ¼ 2; typical field of view (FOV) acquired forthe short axis slices ¼ 350 * 350 mm; breath-hold du-ration ¼ 6–8 heartbeats per slice.

In a subgroup of subjects (n ¼ 13), additional four-chamber and LV outflow-tract (LVOT) slices, as wellas three short-axis cine-SSFP slices, were acquired byusing an HTR of 5.5–6.2 ms. The central short-axisslice was positioned at the midpoint between the LVapex and the coaptation point of the mitral valve leaf-lets on the long-axis view at end-diastole. The basaland apical short-axis slices were equidistant from thecentral slice at end-systole (16–22 mm slice gap, cen-ter to center). Performance at end-systole ensuredthat the LVOT was excluded from the basal slice andthat the apical slice remained well within the imagingplane throughout the cardiac cycle. The image-acqui-sition parameters were as follows: TR/TE/flip angle ¼2.7–3.1 ms/1.35–1.6 ms/55�; acquired voxel size ¼2.0 � 2.0 � 8 mm3; reconstructed voxel size ¼ 1.76 �1.76 � 8 mm3; half-scan factor ¼ 0.625; number ofphase-encoding steps acquired per heartbeat ¼ 2;acquired temporal resolution ¼ 5.5–6.2 ms per car-diac phase. To bring the acquisition time within a rea-sonable breath-hold realm (�18–20 heartbeats), twoacceleration techniques were considered for evalua-tion: 1) SENSE with an acceleration factor of 3 in thephase-encoding direction (typically anterior–posterior¼ 3), and 2) k-t BLAST (without SENSE) with effectiveacceleration factor of 3.8 (k-t factor ¼ 4). The numberof phase-encoding steps required to achieve the pre-scribed spatial resolution was about 175 (350 * 350mm FOV). The combination of half-scan (factor ¼0.625), parallel imaging acceleration (3 [for SENSE],or 3.8 [for k-t BLAST], and segmented k-space

High Temporal Resolution SSFP Cine MRI 873

acquisition [turbo factor ¼ 2]), reduced the numberof heartbeats required to collect all the necessaryphase-encoding steps to around 18–20. The SENSE-accelerated acquisition was retrospectively gatedand the k-t BLAST-accelerated scan was prospec-tively triggered. Thus, depending on the heart rate,120–176 cardiac phases were acquired. All theimages were stored in the Digital Imaging and Com-munications in Medicine standard format (DICOM;NEMA, Rosslyn, VA).

Image Analysis

Manual Image Analysis

All the data were transferred to a commercial postpro-cessing workstation (ViewForum; Philips Healthcare,Andover, MA). An experienced cardiac MR expert (with5 years of clinical cardiovascular MR experience)reviewed the stack of short-axis images and manuallydrew contours to obtain the end-diastolic volume andend-systolic volume from the lower temporal resolu-tion images.

Semiautomated Image Analysis

The LV slice volume was segmented by using a cus-tom-written program in MATLAB (Release 14; v. 7.0.4;MATHWORKS, Natick, MA), which was an adaptationof an existing in-house developed algorithm (21).

LV Volume Calculation: Modified Simpson Algorithm

The total LV volume was calculated by means of themodified Simpson algorithm by using the areas of thethree short-axis slices of the LV instead of the two-slice model described originally (22,23). The totallength of the LV at each phase was manually meas-ured as:

L ¼ L1 þ L2 þ L3 þ L4

where L2 and L3 are the interslice gaps from the basalslice and the apical slice to the mid-cavity slice,respectively. L1 is the distance from the basal slice tothe mitral valve annulus, and L4 is the distance fromthe apical slice to the apex. The total volume (V) of theLV was calculated from the area of the LV cavity inthe basal (Ab), mid (Am), and apical (Aa) slices by usingthe following formula:

V ¼ L1 � Ab þ L2 � ðAb þ AmÞ2

þ L3 � ðAm þ AaÞ2

þ L4 � Aa

3

� �

This method was validated in a subgroup of 20 nor-mal subjects. After validation the total LV volume wascalculated in the remaining 13 subjects at HTR.

Derivation of Diastolic Parameters

Indices of diastolic function were derived from thetotal LV-volume curves, as well as the individual sli-ces (in the basal, mid-cavity, and apical locations)obtained from the HTR cine images as described here.

The LV cavity in each of the three short-axis slicesacquired at HTR was segmented by using the semiau-tomated image-analysis algorithm. From the seg-mented LV volumes the time–volume curve was gener-ated for each of the three slices. In addition, a totalLV–volume curve was generated by using the modifiedSimpson method. The following steps were involved inanalyzing the time–volume curves: 1) the raw seg-mented time–volume curves were smoothed by usinga moving average filter with a kernel size of 3; 2) thederivative of the smoothed time–volume curve wasobtained by using a three-point kernel to perform alinear fit calculation. The slope of the three-point lin-ear fit was taken as the slope of the midpoint. The fol-lowing parameters were derived from the total LVtime–volume curve obtained from SENSE and k-tBLAST imaging techniques (Fig. 1 depicts the parame-ters involved pictorially):

1) Time to end-systole (TES): The time (cardiacphase) when the LV blood volume measured is atits minimum. This time corresponds to a zerocrossing (from a negative to a positive value) ofthe rate of change in the LV volume (dV/dt) curve(24–27). TES is measured as the time intervalfrom the start of acquisition (occurrence of R-wave,corresponding to time t ¼ 0) to the time corre-sponding to zero-crossing in the dV/dt curve.

2) Peak filling rate (PFR) and time to PFR (TPFR):The PFR is defined as the peak value in the dV/dt curve after the occurrence of the TES, ie, whenthe passive (early) filling rate is maximal. The TPFRis the duration between the TES and the PFR.

3) Peak active filling rate (PAFR) and E/AMR ratio:The PAFR is the peak LV filling rate during theactive (late) filling phase. The E/AMR ratio is theratio of the PFR to the PAFR.

4) Peak ejection rate (PER) and time to PER (TPER):The PER is defined as the negative peak in thedV/dt curve before the occurrence of TES, whichindicates the maximal LV ejection rate. TPER isthe time of occurrence of PER.

Figure 1. Analysis of an LV volume–time curve and its corre-sponding rate of change (dV/dt) values. The following dia-stolic parameters were measured: TPER, time to peakejection rate; TES, time to end-systole; TPFR, time to peakfilling rate; TPAFR, time to peak active filling rate; IVRT, iso-volumic relaxation time; PFR, peak filling rate; and PAFR,peak active filling rate.

874 Krishnamurthy et al.

5) Isovolumic Relaxation Time (IVRT): The onset ofthe isovolumic relaxation begins shortly after theTES, when there is minimal LV filling or a near-constant LV volume. The end of the isovolumicrelaxation is characterized by a rapid increase infilling, represented as the local minimum of thedV/dt curve between the TES and the TPFR. Thetime between the onset and end of isovolumicrelaxation is characterized as IVRT.

Effects of the Temporal Sampling Rate onDiastolic Parameters

To study the effects of the temporal sampling rate, thetime–volume curve obtained at the highest temporalresolution (�6 ms) was undersampled by factors of 2,3, 4, 5, and 6 to yield a temporal resolution of 12, 18,24, 30, and 36 ms. Because the acquired temporal re-solution among patients varied from 5.5–6.2 ms,depending on the heart rate, the volume curve wasresampled at a 1-ms temporal resolution by usingpiecewise linear interpolation. From this resampleddata the volume curve was downsampled to temporalresolutions of 12, 18, 24, 30, and 36 ms for subse-quent analysis. The derivative of the time–volumecurve was calculated for the new undersampled data.The data analysis was performed to calculate the newvalues of the diastolic parameters, which were thencompared with the ‘‘6-ms’’ resolution values.

The E/AMR ratio was calculated only for the dataobtained from SENSE imaging, as k-t BLAST acquisi-tion relies on prospective electrocardiographic gatingand does not fully capture the atrial-contractionphase during the cardiac cycle.

Echocardiographic Measurement

In the 13 volunteers who underwent HTR cine imagingof the heart, echocardiographic images (GE Vivid 3; GEMedical Systems, Milwaukee, WI) were also acquiredwithin an hour after the MR examination. Subjects wereplaced in the left lateral decubitus position and stand-ard echocardiographic views were recorded.

The IVRT and the transmitral E and A wave veloc-ities were measured as previously described (28). TheIVRT was measured by using a continuous-waveDoppler technique with the Doppler cursor aligned ina position between the mitral and the aortic valve in

the apical five-chamber view. The E and A velocitieswere obtained by using a pulsed-wave Doppler tech-nique with the sample volume placed at the level ofthe mitral annulus. The transmitral velocities andIVRT were obtained by averaging the results over sixto eight cardiac cycles.

RESULTS

The MR acquisition was performed successfully in all33 subjects. The total LV volume was calculated byusing the modified Simpson algorithm.

Validation of the Modified Simpson Algorithm forEstimation of the Total LV Volume from ThreeShort-Axis Slices

The total LV volume computed by using the modifiedSimpson algorithm on three short-axis slices acquiredfrom the basal, mid, and apical regions was in goodagreement with the total LV volume computed fromendocardial contours manually drawn by an expert ona stack of contiguous short-axis slices by means ofthe disk-summation method in 20 subjects. Theresults show that the percent mean bias and limits ofagreement determined by Bland–Altman analyses forestimation of the EDV, ESV, and EF (�2.8 6 7%, �3.16 �10.3%, and �0.3 6 4.7%, respectively) are in closeagreement with the interobserver and intraobservervariability of the experienced observers (21).

Analysis of LV Time–Volume Curves

The total LV volume measured with the modifiedSimpson approach was used to generate the LV time–volume curves in 13 subjects with HTR cine-SSFPdata. The previously described derivative-basedmethod was used to analyze these curves success-fully. Bland–Altman analyses revealed good agreementbetween the TES, PER, TPER, TPFR, and PFRvalues derived from the SENSE-accelerated and k-tBLAST-accelerated acquisitions. Table 1 summarizesthe actual values and presents the filling and ejectionrates normalized to the end-diastolic volume(expressed as EDV/s). Parameters of atrial function(ie, PAFR and TPAFR) were derived only on the SENSEscans, as the k-t BLAST-accelerated scans missed thedistal portion of end-diastole.

Table 1

Absolute Values of Various Diastolic Functional Indices Derived From the Time-Volume Curves Generated From the SENSE-Accelerated

and k-t BLAST-Accelerated Acquisitions (Mean 6 SD)

TES TPER TPFR PER PFR

(ms) (ms) (ms) (ml/s) � EDV/s (ml/s) � EDV/s

SENSE 301 6 29.1 139 6 49.8 156 6 36 722.4 6 136.5 4.9 6 0.9 723.4 6 144.9 5.0 6 0.9

k-t BLAST 318.5 6 49.8 128.3 6 43.9 163 6 43 750.6 6 155.4 5.5 6 1.0 715.8 6 113.9 5.3 6 0.8

Bland-Altman analysis �17.5 6 30 8.4 6 40.5 �11.5 6 20.9 �26 6 80 �0.6 6 0.7 18.6 6 70.4 �0.36 6 0.69

SENSE, sensitivity encoding; k-t BLAST, spatial frequency-temporal frequency broad-use linear acceleration technique; SD, standard devi-

ation; TES, time to end-systole; TPER, time to peak ejection rate; TPFR, time to peak filling rate; PER, peak ejection rate; PFR, peak fill-

ing rate. PER and PFR are also expressed as normalized with respect to the corresponding end-diastolic volumes and expressed as

EDV/s.

High Temporal Resolution SSFP Cine MRI 875

The analysis of time–volume curves obtained ateach of the three short-axis slice locations revealed adifference in the filling patterns between the curves;this difference reflected regional variations in contrac-tion-relaxation across the LV during the cardiac cycle(Fig. 2). Furthermore, for �45% of the slices from theapical and basal locations there was no discernibleIVRT.

Effect of Temporal Undersampling

Figures 3 and 4 depict the effect of temporal under-sampling of the time–volume curves. With increasingdecimation factors, the local minima used to identifythe onset of the rapid-filling phase disappeared, mak-ing it difficult to estimate the end of the IVRT (Fig. 3).Calculation of the cardiac phase where the end ofIVRT occurred failed for temporal resolutions �18 ms.As the temporal resolution worsened, there was a pro-gressive decline in the ability to estimate all the fillingrates (ie, PER, PFR, and PAFR) (Fig. 4, Table 2), andthis decline was significant between the filling rates atall temporal resolutions.

Comparison of the IVRT and the E/A Ratio WithEchocardiography Versus MR

The IVRT values derived from the MR-based LV time–volume curves were in broad agreement with esti-mates of the IVRT derived from echocardiography,having a mean bias of �0.4 6 13 ms and �6 6 16 mswith SENSE and k-t BLAST, respectively (Fig. 5). Thecomparison was performed for 12 volunteers, as theIVRT values could not be obtained for one volunteerby means of echocardiography, although the E/A ratiowas obtained for all 13 volunteers.

The mean E/A ratio calculated from the time–vol-ume curves obtained with MRI was 2.2 6 1.0, andthat obtained with Doppler echocardiography was1.89 6 0.9. Although the E/AMR was in the samerange as the E/A obtained echocardiographically, thetwo values were significantly different from each other(P ¼ 0.43).

DISCUSSION

The results of this study show that with modern mul-tichannel MR hardware and acceleration techniquessuch as SENSE or k-t BLAST it is feasible to obtaincardiac cine MR images at a temporal resolution onthe order of a few milliseconds (approaching the limitsof the repetition time) without compromising the spa-tial or contrast resolution. A number of issues are

Figure 2. Normalized regional LV volumes of individual api-cal, mid-cavity, and basal slices, as well as the total LV vol-ume computed from these three slices. The asterisksindicate the time to end-systole (TES), as computed by thedata-analysis algorithm. Note the substantial regional varia-tion in LV contraction-relaxation across the slice locations.

Figure 3. Effect of subsampling on estimation of the IVRT.The algorithm fails to determine the isovolumic relaxationperiod at lower temporal resolutions (�18 ms). LV, left ven-tricular. Top: Representative time–volume curve at a resolu-tion of 6 ms. Center: Corresponding rate of change in the LVvolume (dV/dt) at different sampling rates. Bottom: Enlargedversion of the dV/dt values during the isovolumic phase.Note the complete disappearance of the local minima afterthe TES, indicating the end of the IVRT at temporal resolu-tions of �18 ms (solid arrow). Also note the progressivedecline in the peak filling rate from 6–24 ms (double arrows).

876 Krishnamurthy et al.

worth discussing regarding the estimation of clinicallyrelevant quantitative parameters from these HTRdata.

First, one of the challenges in processing HTR cine-SSFP images is the need to delineate the LV cavity forvolumetric analysis. Manual contouring of more than100 phases per slice would be prohibitively time-con-suming and, thus, not usable in routine clinical prac-tice. Therefore, the clinical adoption of HTR cine-SSFPimaging necessitates that some degree of automationbe used for LV segmentation. Our LV-segmentationalgorithm utilizes a bimodal histogram of the cine-SSFP images along with the convexity of the LV cavity;the margin of error in segmenting various sections ofthe LV was within reasonable limits (21). The currentsemiautomated processing approach, including thepreviously described manual region of interest (ROI)-selection process, takes about 90 seconds per slice ona modern desktop personal computer (ie, a 2.80-GHzIntel Xeon processor with 3 GB of RAM). With optimi-zation, this time could be further reduced.

Second, acquiring HTR cine-SSFP images that coverthe entire LV with contiguous short-axis slices neces-sitating one breath-hold per slice may not be clinicallypractical. Therefore, models are needed that wouldaccurately predict the LV volume on the basis of mini-mum data acquisition. Thiele et al (22) have experi-mented with various mathematical models for esti-mating LV volumes by using as few as two slices. Inour study we extended the modified Simpson model

from two slices to three. Our results showed that thetotal LV volume computed from the modified three-slice approach was very close to that obtained by anexpert observer with the stack of contiguous slicescovering the entire LV. The three-slice approach reliedon fewer assumptions regarding the LV shape andallowed us to assess the regional differences in the LVfilling and relaxation parameters. We speculate thatthe three-slice approach may prove to be more robustthan the two-slice method for evaluating LV volumesin a clinical setting, where one would encounter awide variety of LV shapes.

Third, the k-t BLAST approach, unlike the SENSEapproach, exploits redundancies in information inboth the spatial and temporal domains. Nevertheless,the results of our study confirmed that key metricsderived from the time–volume curves obtained withSENSE or k-t BLAST techniques were in good agree-ment. Two points are worth noting in regard to the k-tBLAST technique. 1) For the acceleration factor usedin this study (3.8), the spatiotemporal undersamplingintrinsic to k-t BLAST acquisition did not appear todegrade the temporal fidelity of the time–volumecurves. The undersampling might become a majorsource of temporal blurring at higher acceleration fac-tors, and it needs to be carefully considered. 2)Although this is not an intrinsic limitation of the tech-nique itself, current implementation of k-t BLASTrequires prospective cardiac gating, which missesabout 5%–10% of end-diastole. This makes it difficultto estimate parameters that characterize atrial fillingsuch as the PAFR. On the other hand, the SENSEtechnique uses retrospective gating and acquires datathroughout the cardiac cycle. In addition, SENSErelies on the redundancy of coil-sensitivity informa-tion in the spatial domain, so it does not have anypotential limitation with respect to temporal blurring.Therefore, the SENSE-accelerated technique may bemore suitable for assessing diastolic functional indi-ces derived from LV-volume filling patterns. It shouldbe noted that SENSE acquisition, in particular, greatlybenefited from the 32-channel RF coil array that weused for imaging. The 32-channel configuration allowspotential for SENSE acceleration along the RL, AP,and FH directions because of its coil geometry. There-fore, independent of the orientation of the heart withinthe thoracic cavity, this coil geometry permits higherSENSE acceleration factors. We have previouslyshown that cardiac cine SSFP images acquired byusing a 5-channel coil with a SENSE acceleration fac-tor of 2 yielded LV volumes with sufficient signal-to-

Figure 4. Progressive decline in filling rates with worseningtemporal resolution. The filling rates shown are absolute val-ues. For values normalized to the end-diastolic volume, seeTable 2. PER, peak ejection rate; PFR, peak filling rate;PAFR, peak active filling rate.

Table 2

Variation of Filling and Ejection Rates With Temporal Resolution (Mean 6 SD)

6 ms 12 ms 18 ms 24 ms 30 ms 36 ms

PER (ml/s) 724 6 131 592 6 96 564 6 96 547 6 92 533 6 83 512 6 73

� EDV/s 4.9 6 0.9 4.1 6 0.8 3.9 6 0.8 3.8 6 0.8 3.7 6 0.7 3.6 6 0.7

PFR (ml/s) 734 6 144 635 6 96 614 6 93 588 6 87 566 6 84 544 6 93

� EDV/s 5.0 60.9 4.3 6 0.6 4.2 6 0.6 4.1 6 0.6 3.9 6 0.5 3.8 6 0.5

PAFR (ml/s) 420 6 123 331 6 92 304 6 90 283 6 74 268 6 74 262 6 87

� EDV/s 2.8 6 0.9 2.2 6 0.6 2.1 6 0.6 1.9 6 0.5 1.9 6 0.5 1.8 6 0.6

SD, standard deviation; PER, peak ejection rate; PFR, peak filling rate; PAFR, peak active filling rate.

High Temporal Resolution SSFP Cine MRI 877

noise ratio (SNR) that are comparable to conventionalcardiac cine acquisitions without SENSE (29). How-ever, our previous efforts to obtain similar-quality 2Dcine images with a 5-channel coil array at accelera-tion factors greater than 2 were significantly limitedby the available SNR.

Fourth, the metrics that characterize the filling pat-terns derived from the mid-ventricular slices corre-sponded closely with those derived from the total LV–volume curves. On the other hand, the filling patternsof the LV basal slice varied qualitatively from those ofthe mid-cavity and apical slices. The basal slice typi-cally had a longer TES than did the mid-cavity andapical slices (Fig. 2). Determination of the IVRT fromthe data-analysis algorithm failed in nearly half(45%) of the basal and apical slices, as the isovolu-mic phase was entirely indiscernible from the time–volume curves. Instead, at the basal and apical loca-tions the regional volume curves simply had a sus-tained gradual reduction in LV volume throughoutthe isovolumic phase, resulting in a prolonged TEScompared to that of the mid-ventricular volumecurve or the total volume curve. This finding sug-gests that, whereas there was very little change inthe total LV volume during the isovolumic phase,there were shape changes along the LV length at dif-ferent LV locations. We speculate that these changes

were perhaps due to the differences in the regionalcontraction patterns across the length of the LVthroughout the cardiac cycle. Such a regional varia-tion in contraction patterns has also been reportedwith regard to strain-encoded MRI and other meth-ods (30–32). For example, Zwanenburg et al (32), aswell as other investigators (30), have shown that incomparison with the basal and apical slices, themid-cavity slice undergoes the least longitudinalstrain and that its maximal radial strain rate corre-sponds more closely with mitral valve closure. Ourresults also suggest a similar phenomenon, in whichthe TES of the mid-cavity slice is closest to the TEScalculated for the entire LV volume. Hamdan et al(30) reported that the onset of peak circumferentialand radial strain, as well as maximal strain, variesacross the basal, mid, and apical portions of the LV.

Fifth, after sampling a signal at a high frame rate, itis possible to subsample the acquired data to studythe effect of temporal resolution on the derivation ofquantitative metrics. Our study showed that determi-nation of the IVRT by using the above-described anal-ysis algorithm fails for all temporal resolutions of �18ms. The normal IVRT is �80 ms, and conventionalcine MR acquisition with a temporal resolution of 30–50 ms is insufficient to accurately capture such atransient phenomenon. Moreover, we noticed a pro-gressive decline in all the filling rates as the temporalresolution worsened. For example, the PFR declinedfrom 724 6 131 ml/s (5.0 6 0.9 EDV/s) at a temporalresolution of 6 ms to 544 6 93 ml/s (3.8 6 0.5 EDV/s) at a temporal resolution of 36 ms. These resultssuggest that the temporal resolution is a key parame-ter that needs to be taken into account when estimat-ing the filling or ejection rates. For example, previousinvestigators (33,34) who used lower-temporal-resolu-tion MRI and other researchers (9,35,36) reported fill-ing and ejection rates that were substantially less(PFR �3.3 6 0.6 EDV/s) than those observed in ourstudy. Our results suggest that such reductions inthe filling and ejection rates arise from a lower tempo-ral resolution. A similar decline was evident for thePER and PAFR. Moreover, the time of occurrence ofevents such as the TPFR, TPER, and TAFR was scaledwith the temporal resolution of the acquisition.

Sixth, our study showed that IVRT values measuredfrom echocardiograms versus the total LV-volumecurves obtained from MR images were in close agree-ment (Fig. 5). With these methods, derivation of theIVRT relies on two distinct approaches. Whereasechocardiography measures the IVRT as the timebetween aortic valve closure and the onset of transmi-tral flow, MRI measures it as the duration of theslowly varying volume period obtained from the time–volume curve after occurrence of the TES. In the long-axis view, valve closure and opening may conceivablybe used to directly estimate an echo-analog for theIVRT, but our initial efforts to identify the exact onsetof valve opening or closure were unsuccessful due topoor contrast between the valve leaflets and the sur-rounding blood.

Finally, computation of the E/AMR ratio in MRI isfundamentally distinct from computation of this

Figure 5. Bland–Altman analysis of IVRTs obtained with MRversus ECHO (echocardiography). Views A and B comparethe IVRTs obtained with the SENSE and k-t BLAST imagingtechniques for the total volume.

878 Krishnamurthy et al.

parameter in echocardiography. The MRI estimatesrely on the total LV filling rates, whereas echocardio-graphic estimates rely on the peak velocity measure-ment in the early and late filling phases across themitral valve. Numerous investigators have attemptedto compute E/AMR ratios from phase-contrast meas-urements performed across the mitral valve. To thebest of our knowledge, however, we are the first todescribe an LV volume-based method for estimatingthe E/AMR ratio at HTR.

In conclusion, cardiac MRI (CMRI) is regarded asthe gold standard in the assessment of LV systolicfunction. Investigators have also used various MRIsequences (eg, tissue tagging and displacementencoding with stimulated echoes [DENSE] imaging) toevaluate LV diastolic function. Nevertheless, thesemethods are often too time-consuming and labor-in-tensive for use in data acquisition and analysis. Wehave shown that it is possible to obtain cine-SSFPimages with a temporal resolution of �6 ms by usingmodern multichannel MR hardware and appropriateacceleration techniques such as SENSE and k-tBLAST. The analysis can be performed in less than 2minutes by using a personal computer semiautomati-cally. However, there is a progressive decline in the LVfilling rates at poorer temporal resolutions, and tran-sient phenomena (such as the IVRT) that occur duringthe cardiac cycle are difficult to characterize with tem-poral resolutions of �18 ms.

Further work will be necessary to establish normalreference values for indices such as the PFR for clini-cal use, and for comparison with echocardiography inassessing patients who have ischemic and nonische-mic cardiomyopathy involving various stages of dia-stolic dysfunction. When combined with delayedenhancement MR, CMRI could potentially offer a com-prehensive assessment of systolic and diastolic functionin a single setting without a prolonged imaging time.

ACKNOWLEDGMENTS

The authors thank Mercedes Pereyra, RT, DebraDees, RN, and Brenda Lambert, RN, for their assis-tance in performing the study. We also thank VirginiaFairchild, of the Texas Heart Institute’s Department ofScientific Publications, for editorial assistance.

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