in recent years there has been a significant increase in in vivo imaging studies of experimental rodents .
this has been driven by several factors , including the desirability of non - invasive , longitudinal examinations of disease progression , the availability of genetically modified animals , and technological developments enabling the translation of clinical imaging techniques to the animal laboratory .
magnetic resonance imaging ( mri ) is particularly versatile , providing anatomical , functional , and dynamic information , and is now widely established for the imaging of rats and mice , including cardiac studies [ 25 ] .
the main drawback to mri is the examination time , which is typically 1  h or more per animal .
such prolonged periods of anaesthesia are potentially harmful to small animals , especially when imaged shortly after surgical intervention ( e.g. , for induction of myocardial infarct ) , requiring careful monitoring during subsequent recovery periods .
shorter scan times would improve animal welfare by reducing this exposure to anaesthesia , would minimise the effects of physiological instability during scanning , and would also reduce study costs .
mri can be accelerated by acquiring less than the conventional number of rows of k - space .
two different approaches are possible . in so - called  parallel imaging  , ambiguities of reconstruction are resolved by using prior information on the spatial sensitivity patterns of multiple receiver coils [ 6 , 7 ] . in a second class of techniques ,
particularly applicable to dynamic scanning , undersampling of kt - space exploits spatiotemporal correlations in periodic data [ 811 ] and does not require special receiver coils . in a third class of techniques , wech et al .  
recently demonstrated threefold acceleration of mouse cardiac imaging using a compressed sensing   approach to exploit sparsity in the raw data .
the various techniques have achieved accelerations of typically two to four times , and may be combined .
parallel imaging using phased array receiver coils is now widely used to reduce scan times in clinical mri , whereas dynamic undersampling is less well established .
there have been very few reports of translating the undersampling techniques to the imaging of experimental animals .
the additional challenges of small animal imaging include limited signal - to - noise ratio ( snr ) and the difficulty of designing non - interacting rf coils for parallel acquisition at the high frequencies encountered in typical preclinical scanners ( 200  mhz and above ) . despite these difficulties , parallel imaging in rat   and mouse   cardiac studies have recently been demonstrated by schneider et al .
have also demonstrated parallel imaging to accelerate mr angiography in mice . in this work ,
we explored the feasibility of the kt - broad - use linear acquisition speed - up technique ( kt - blast )   acceleration of mouse cardiac imaging .
we first subsampled existing full k - space datasets to determine a suitable acceleration factor , and then implemented accelerated scanning on a small animal scanner .
conventional and accelerated cardiac images were compared qualitatively and by determination of standard cardiological indices in both healthy and myocardial infarcted animals .
male 1012  week old c57bl/6 mice ( n  =  9 ) were anaesthetised with isoflurane at 1.5    0.3  % to maintain respiration at 5060 breaths per minute as monitored by a pressure pad .
heart - rate was monitored from ecg recorded using needle electrodes inserted subdermally on either side of the heart ( small animal instruments inc . ,
rectal temperature was maintained at 37  c by a hot air blower with feedback control .
animals were scanned using a 7 t mri system ( agilent technologies , formerly varian inc . ) with a 39-mm quadrature coil .
the cardiac short - axis was identified from a series of localiser scans broadly as described by schneider et al . .
cine sequence ( tr / te  =  7.3/2.7  ms , flip angle 15 ) with gradient and rf spoiling , consisting of 1213 time frames , 9 contiguous slices of 1  mm thickness , fov 30  mm , a 192    192 matrix and 4 averages .
kt - blast simulations written in matlab consisted of selecting rows of k - space from 12 time frames to represent  training  data ( central 16 rows ) and  r - fold accelerated acquisition  data ( every rth row of k - space , where r  =  [ 24 , 6 ] and the index of the first row is incremented between time frames ) . training and accelerated data were used to reconstruct image sets using the standard kt - blast algorithm . the magnitude
 between reconstruction from full k - space and from undersampled k - space , normalised to the values from the full reconstruction , was calculated for a 60    60 pixel region of interest ( roi ) placed around the heart and averaged over all slices , time frames and pixels for a given animal and acceleration .
mathematically,1\documentclass[12pt]{minimal } 
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				 \begin{document}$$ \varepsilon = \frac{1}{nt \times ns \times nx \times ny}\sum { \frac{{\left| { i_{f } - i_{u } } \right|}}{{i_{f } } } } $ $ \end{document}where nt , ns , nx and ny are respectively the numbers of time frames , slices , pixels in the x - direction and pixels in the y - direction within the roi .
if refers to the image reconstructed from full k - space and iu that from undersampled k - space .
the summation is over all t , s , x and y. this roi size was chosen to capture ghosting artefacts from undersampling which are expected to appear both inside and outside the heart .
cardiological indices of left ventricular function ( end diastolic volume edv , end systolic volume esv , stroke volume sv , ejection fraction ef , end diastolic mass edm , end systolic mass esm ) were measured from all image sets by one experienced analyst who was blinded to the identity of each set .
measurements were made by drawing around epicardial and endocardial boundaries in imagej software ( http://rsbweb.nih.gov/ij ) .
the papillary muscles were excluded from the lv blood pool , and a density of 1.05  g / cm was assumed for the myocardium .
a subjective rating of quality was also given to each set , ranging from 1 (  poor  ) through to 5 (  good  ) .
this subjective rating was based on a combination of apparent snr , severity of artefacts , delineation of the myocardium and ease of measurement .
after unblinding , two - tailed t tests were used to determine whether the cardiological indices measured at each acceleration factor were significantly different ( p  <  0.05 ) from those measured using full k - space reconstruction
. a suitable acceleration factor of three was determined from the simulated undersampling experiments ( see  results  section ) .
kt - blast undersampling with this acceleration factor was implemented on the scanner , together with a training sequence that acquired the central 16 rows of k - space . a further 6 mice ( body weights 2855  g )
were each imaged with ( i ) the standard cine sequence as above , except that the heart was covered in 8 slices with three signal averages being acquired ( cine-3 ) ; ( ii ) the kt - blast undersampling and training sequences as implemented ( ktb-3 ) , each with three signal averages ; ( iii ) the standard sequence but with only one signal average ( cine-1 ) .
the accelerated sequence with pathology , 6 mice in which myocardial infarct had been induced by permanent ligation of the left anterior descending coronary artery   were scanned with this protocol ( five only with the cine-1 sequence ) between 4 and 7  days after induction of infarct .
the infarcted mice ( body weights 2230  g ) were scanned using a 33  mm coil .
acquisition time was approximately 20  min for the full cine sequence , and 7  min each for the undersampling sequence and cine sequence with one average .
all image sets were reconstructed , scored qualitatively , and the cardiological indices measured as above , with the analyst again being blinded to their identity .
after unblinding , the cardiological indices for each animal measured with the accelerated scan and the cine scan with one average were compared using bland 
the contrast to noise ratio ( cnr ) between the left ventricular blood pool and the myocardium was determined using the relationship cnr  =  ( sblood    smyo)/ where sblood is the mean signal level in the left ventricle , smyo is the mean signal level in the septum , and  is the combined ( square root of sum of squares ) standard deviation of smyo and sblood , all measured on a mid - ventricular slice at end diastole .
male 1012  week old c57bl/6 mice ( n  =  9 ) were anaesthetised with isoflurane at 1.5    0.3  % to maintain respiration at 5060 breaths per minute as monitored by a pressure pad .
heart - rate was monitored from ecg recorded using needle electrodes inserted subdermally on either side of the heart ( small animal instruments inc . ,
rectal temperature was maintained at 37  c by a hot air blower with feedback control .
animals were scanned using a 7 t mri system ( agilent technologies , formerly varian inc . ) with a 39-mm quadrature coil .
the cardiac short - axis was identified from a series of localiser scans broadly as described by schneider et al . .
cine sequence ( tr / te  =  7.3/2.7  ms , flip angle 15 ) with gradient and rf spoiling , consisting of 1213 time frames , 9 contiguous slices of 1  mm thickness , fov 30  mm , a 192    192 matrix and 4 averages .
kt - blast simulations written in matlab consisted of selecting rows of k - space from 12 time frames to represent  training  data ( central 16 rows ) and  r - fold accelerated acquisition  data ( every rth row of k - space , where r  =  [ 24 , 6 ] and the index of the first row is incremented between time frames ) . training and accelerated data were used to reconstruct image sets using the standard kt - blast algorithm . the magnitude
 between reconstruction from full k - space and from undersampled k - space , normalised to the values from the full reconstruction , was calculated for a 60    60 pixel region of interest ( roi ) placed around the heart and averaged over all slices , time frames and pixels for a given animal and acceleration .
mathematically,1\documentclass[12pt]{minimal } 
				 \usepackage{amsmath } 
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				 \begin{document}$$ \varepsilon = \frac{1}{nt \times ns \times nx \times ny}\sum { \frac{{\left| { i_{f } - i_{u } } \right|}}{{i_{f } } } } $ $ \end{document}where nt , ns , nx and ny are respectively the numbers of time frames , slices , pixels in the x - direction and pixels in the y - direction within the roi .
if refers to the image reconstructed from full k - space and iu that from undersampled k - space .
the summation is over all t , s , x and y. this roi size was chosen to capture ghosting artefacts from undersampling which are expected to appear both inside and outside the heart .
cardiological indices of left ventricular function ( end diastolic volume edv , end systolic volume esv , stroke volume sv , ejection fraction ef , end diastolic mass edm , end systolic mass esm ) were measured from all image sets by one experienced analyst who was blinded to the identity of each set .
measurements were made by drawing around epicardial and endocardial boundaries in imagej software ( http://rsbweb.nih.gov/ij ) .
the papillary muscles were excluded from the lv blood pool , and a density of 1.05  g / cm was assumed for the myocardium .
a subjective rating of quality was also given to each set , ranging from 1 (  poor  ) through to 5 (  good  ) .
this subjective rating was based on a combination of apparent snr , severity of artefacts , delineation of the myocardium and ease of measurement .
after unblinding , two - tailed t tests were used to determine whether the cardiological indices measured at each acceleration factor were significantly different ( p  <  0.05 ) from those measured using full k - space reconstruction .
a suitable acceleration factor of three was determined from the simulated undersampling experiments ( see  results  section ) .
kt - blast undersampling with this acceleration factor was implemented on the scanner , together with a training sequence that acquired the central 16 rows of k - space . a further 6 mice ( body weights 2855  g )
were each imaged with ( i ) the standard cine sequence as above , except that the heart was covered in 8 slices with three signal averages being acquired ( cine-3 ) ; ( ii ) the kt - blast undersampling and training sequences as implemented ( ktb-3 ) , each with three signal averages ; ( iii ) the standard sequence but with only one signal average ( cine-1 ) .
the accelerated sequence with pathology , 6 mice in which myocardial infarct had been induced by permanent ligation of the left anterior descending coronary artery   were scanned with this protocol ( five only with the cine-1 sequence ) between 4 and 7  days after induction of infarct .
the infarcted mice ( body weights 2230  g ) were scanned using a 33  mm coil .
acquisition time was approximately 20  min for the full cine sequence , and 7  min each for the undersampling sequence and cine sequence with one average .
all image sets were reconstructed , scored qualitatively , and the cardiological indices measured as above , with the analyst again being blinded to their identity .
after unblinding , the cardiological indices for each animal measured with the accelerated scan and the cine scan with one average were compared using bland 
the contrast to noise ratio ( cnr ) between the left ventricular blood pool and the myocardium was determined using the relationship cnr  =  ( sblood    smyo)/ where sblood is the mean signal level in the left ventricle , smyo is the mean signal level in the septum , and  is the combined ( square root of sum of squares ) standard deviation of smyo and sblood , all measured on a mid - ventricular slice at end diastole .
figure  1 shows representative mid - ventricular images at early systole from the simulated acceleration study .
the reconstruction error  , averaged over all animals ( n  =  9 ) , increased , and the subjective quality rating decreased as the simulated acceleration factor r increased ( table  1 ) .
the effect of simulated acceleration on the measured cardiological parameters is shown in table  1 and fig .  2 .
notably , as the acceleration factor was increased , measured esv increased whilst measured edv was approximately maintained .
consequently , the estimated stroke volume and ejection fraction fell from their  true  values measured from full k - space data , with the difference reaching statistical significance for r  =  6 .
1representative mouse cardiac images at end diastole reconstructed using full k - space data ( a ) and simulated fourfold kt - blast undersampling ( b ) ; magnitude difference image between ( a ) and ( b ) , displayed with the same ( c ) and with threefold expanded windowing ( d ) to emphasise the differences .
the roi for error analysis is indicated . in this example , the calculated reconstruction error  was 0.53 .
good  for the full reconstruction and  reasonable  for the fourfold undersampled reconstruction .
scale bar 10  mmtable  1simulated kt - blast accelerationacceleration factorerror  
 quality ( q)edv ( l)esv ( l)sv ( l)ef ( % ) edm ( mg)esm ( mg)1 ( full k - space)0.004.2    1.162    1025    638   
760    8108    10123    1320.32    0.063.7    1.163    1226    536    858    6107    13120    1330.39    0.063.1    0.6 * 61    1027    734   
656    7114    13126    1340.45    0.072.4    1.1 * 62    1128    534    854    7108    13125    1560.55    0.081.1    0.3 * 59    830    629    4 * 49    6 * 
 108    14124    15reconstruction error (  : see text ) , subjective image quality rating ( q ) , and cardiological indices of left ventricular function ( mean    standard deviation ) in healthy mice ( n  =  9 ) measured from images with simulated kt - blast acceleration .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the full k  space values .
2cardiological indices of left ventricular function in healthy mice ( n  =  9 ) measured from images with simulated acceleration , plotted against acceleration factor . edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
see also table  1 
  representative mouse cardiac images at end diastole reconstructed using full k - space data ( a ) and simulated fourfold kt - blast undersampling ( b ) ; magnitude difference image between ( a ) and ( b ) , displayed with the same ( c ) and with threefold expanded windowing ( d ) to emphasise the differences .
the roi for error analysis is indicated . in this example , the calculated reconstruction error  was 0.53 .
good  for the full reconstruction and  reasonable  for the fourfold undersampled reconstruction .
scale bar 10  mm simulated kt - blast acceleration reconstruction error (  : see text ) , subjective image quality rating ( q ) , and cardiological indices of left ventricular function ( mean    standard deviation ) in healthy mice ( n  =  9 ) measured from images with simulated kt - blast acceleration .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the full k  space values .
2 
  cardiological indices of left ventricular function in healthy mice ( n  =  9 ) measured from images with simulated acceleration , plotted against acceleration factor . edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
see also table  1 
  figures  3 and 4 show mid - ventricular images from a healthy and myocardial infarct animal respectively , acquired with the standard ( three average ) , the single - average and the kt - blast accelerated scans .
the cine-1 images are noticeably noisier than the others . table  2 and figs . 
5 and 6 show the group results for the measured cardiological parameters compared to the measurements made from the standard cine sequence .
table  2 also shows the cnr measurements and subjective quality ratings for these scans , which were significantly different from the standard sequence only for the cine-1 sequence applied to healthy mice . as in the simulations ,
kt - blast acceleration led to overestimation of esv and underestimation of sv and ef , but the differences did not reach significance .
a direct comparison between cine-1 and kt - blast results ( table  3 ; fig .  7 ) revealed no significant differences.fig . 
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
scale bar 10  mmtable  2accelerated imaging resultsscancnrquality ( q)edv bias ( l)esv bias ( l)sv bias ( l)ef bias ( % ) edm bias ( mg)esm bias ( mg)healthycine-33.4    0.84.0    1.3cine-12.9    0.62.3    1.2*4.7    12.01.5    8.23.3    7.30.2    6.47.3    12.53.9    11.6ktb-33.0   
0.73.5    1.55.9    8.81.8    5.37.7    6.04.9    4.611.7    11.20.0    9.4infarctcine-34.9    1.14.5    0.8cine-14.6    1.03.6    0.91.6 
  3.60.2    4.81.8    2.70.8    2.76.7    7.40.7    3.7ktb-33.6    0.6 * 4.0    0.62.4    2.83.2    6.25.6    5.54.1    4.16.1    13.90.9    8.0blood - to - myocardium cnr , subjective image quality rating ( q ) and bias from bland 
altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 or 6 mice with myocardial infarct ) measured from cine images acquired with one signal average ( cine-1 ; 5 mi mice ) and threefold kt - blast acceleration ( ktb-3 ; 6 mi mice ) , compared to the values measured from standard cine images acquired with three signal averages ( cine-3 ; 6 mi mice ) .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the corresponding cine-3 values .
5bland  altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 6 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
6bland  altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from cine images with one signal average ( cine-1 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
see also table  2 
 table  3comparison between ktb-3 and cine-1edv bias ( l)esv bias ( l)sv bias ( l)ef bias ( % ) edm bias ( mg)esm bias ( mg)healthy1.1    6.93.3    4.04.4    5.64.7    4.04.3    11.03.9    11.2infarct0.5    3.44.7    1.65.2    4.14.4    2.90.4    10.11.4    7.3bias from bland 
altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 mice with myocardial infarct ) measured from cine images acquired with threefold kt - blast acceleration ( ktb-3 ) compared with images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
7bland  altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and cine images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . dashed lines indicate bias and dotted lines indicate  2 sd .
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
scale bar 10  mm accelerated imaging results blood - to - myocardium cnr , subjective image quality rating ( q ) and bias from bland 
altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 or 6 mice with myocardial infarct ) measured from cine images acquired with one signal average ( cine-1 ; 5 mi mice ) and threefold kt - blast acceleration ( ktb-3 ; 6 mi mice ) , compared to the values measured from standard cine images acquired with three signal averages ( cine-3 ; 6 mi mice ) .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the corresponding cine-3 values .
altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 6 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from cine images with one signal average ( cine-1 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 mice with myocardial infarct ) measured from cine images acquired with threefold kt - blast acceleration ( ktb-3 ) compared with images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
7 
  bland  altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and cine images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
figure  1 shows representative mid - ventricular images at early systole from the simulated acceleration study .
the reconstruction error  , averaged over all animals ( n  =  9 ) , increased , and the subjective quality rating decreased as the simulated acceleration factor r increased ( table  1 ) .
the effect of simulated acceleration on the measured cardiological parameters is shown in table  1 and fig .  2 .
notably , as the acceleration factor was increased , measured esv increased whilst measured edv was approximately maintained .
consequently , the estimated stroke volume and ejection fraction fell from their  true  values measured from full k - space data , with the difference reaching statistical significance for r  =  6 .
1representative mouse cardiac images at end diastole reconstructed using full k - space data ( a ) and simulated fourfold kt - blast undersampling ( b ) ; magnitude difference image between ( a ) and ( b ) , displayed with the same ( c ) and with threefold expanded windowing ( d ) to emphasise the differences .
the roi for error analysis is indicated . in this example , the calculated reconstruction error  was 0.53 .
good  for the full reconstruction and  reasonable  for the fourfold undersampled reconstruction .
scale bar 10  mmtable  1simulated kt - blast accelerationacceleration factorerror  
 quality ( q)edv ( l)esv ( l)sv ( l)ef ( % ) edm ( mg)esm ( mg)1 ( full k - space)0.004.2    1.162    1025    638   
760    8108    10123    1320.32    0.063.7    1.163    1226    536    858    6107    13120    1330.39    0.063.1    0.6 * 61    1027    734   
656    7114    13126    1340.45    0.072.4    1.1 * 62    1128    534    854    7108    13125    1560.55    0.081.1    0.3 * 59    830    629    4 * 49    6 * 
 108    14124    15reconstruction error (  : see text ) , subjective image quality rating ( q ) , and cardiological indices of left ventricular function ( mean    standard deviation ) in healthy mice ( n  =  9 ) measured from images with simulated kt - blast acceleration .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the full k  space values .
2cardiological indices of left ventricular function in healthy mice ( n  =  9 ) measured from images with simulated acceleration , plotted against acceleration factor . edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
see also table  1 
  representative mouse cardiac images at end diastole reconstructed using full k - space data ( a ) and simulated fourfold kt - blast undersampling ( b ) ; magnitude difference image between ( a ) and ( b ) , displayed with the same ( c ) and with threefold expanded windowing ( d ) to emphasise the differences .
the roi for error analysis is indicated . in this example , the calculated reconstruction error  was 0.53 .
good  for the full reconstruction and  reasonable  for the fourfold undersampled reconstruction .
scale bar 10  mm simulated kt - blast acceleration reconstruction error (  : see text ) , subjective image quality rating ( q ) , and cardiological indices of left ventricular function ( mean    standard deviation ) in healthy mice ( n  =  9 ) measured from images with simulated kt - blast acceleration .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the full k  space values .
2 
  cardiological indices of left ventricular function in healthy mice ( n  =  9 ) measured from images with simulated acceleration , plotted against acceleration factor . edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
figures  3 and 4 show mid - ventricular images from a healthy and myocardial infarct animal respectively , acquired with the standard ( three average ) , the single - average and the kt - blast accelerated scans .
the cine-1 images are noticeably noisier than the others . table  2 and figs . 
5 and 6 show the group results for the measured cardiological parameters compared to the measurements made from the standard cine sequence .
table  2 also shows the cnr measurements and subjective quality ratings for these scans , which were significantly different from the standard sequence only for the cine-1 sequence applied to healthy mice . as in the simulations ,
kt - blast acceleration led to overestimation of esv and underestimation of sv and ef , but the differences did not reach significance .
. a direct comparison between cine-1 and kt - blast results ( table  3 ; fig .  7 ) revealed no significant differences.fig . 
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
scale bar 10  mmtable  2accelerated imaging resultsscancnrquality ( q)edv bias ( l)esv bias ( l)sv bias ( l)ef bias ( % ) edm bias ( mg)esm bias ( mg)healthycine-33.4    0.84.0    1.3cine-12.9    0.62.3    1.2*4.7    12.01.5    8.23.3    7.30.2    6.47.3    12.53.9    11.6ktb-33.0    0.73.5    1.55.9    8.81.8    5.37.7   
6.04.9    4.611.7    11.20.0    9.4infarctcine-34.9    1.14.5    0.8cine-14.6 
  1.03.6    0.91.6    3.60.2    4.81.8    2.70.8    2.76.7    7.40.7    3.7ktb-33.6 
  0.6 * 4.0    0.62.4    2.83.2    6.25.6    5.54.1    4.16.1    13.90.9    8.0blood - to - myocardium cnr , subjective image quality rating ( q ) and bias from bland 
altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 or 6 mice with myocardial infarct ) measured from cine images acquired with one signal average ( cine-1 ; 5 mi mice ) and threefold kt - blast acceleration ( ktb-3 ; 6 mi mice ) , compared to the values measured from standard cine images acquired with three signal averages ( cine-3 ; 6 mi mice ) .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the corresponding cine-3 values .
5bland  altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 6 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
6bland  altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from cine images with one signal average ( cine-1 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
see also table  2 
 table  3comparison between ktb-3 and cine-1edv bias ( l)esv bias ( l)sv bias ( l)ef bias ( % ) edm bias ( mg)esm bias ( mg)healthy1.1    6.93.3    4.04.4    5.64.7    4.04.3    11.03.9    11.2infarct0.5    3.44.7    1.65.2   
4.14.4    2.90.4    10.11.4    7.3bias from bland  altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 mice with myocardial infarct ) measured from cine images acquired with threefold kt - blast acceleration ( ktb-3 ) compared with images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
7bland  altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and cine images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
upper row acquired at end diastole and lower row at end systole . left to right standard cine sequence with three signal averages ( cine-3 ) ; cine sequence with one signal average ( cine-1 ) ; kt - blast reconstruction of a threefold undersampled sequence ( ktb-3 ) .
scale bar 10  mm accelerated imaging results blood - to - myocardium cnr , subjective image quality rating ( q ) and bias from bland 
altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 or 6 mice with myocardial infarct ) measured from cine images acquired with one signal average ( cine-1 ; 5 mi mice ) and threefold kt - blast acceleration ( ktb-3 ; 6 mi mice ) , compared to the values measured from standard cine images acquired with three signal averages ( cine-3 ; 6 mi mice ) .
the range of q is from 1 (  poor  ) through to 5 (  good  ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass . *  significantly different ( p  <  0.05 ) from the corresponding cine-3 values .
altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 6 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from cine images with one signal average ( cine-1 ) and standard cine images acquired with three signal averages ( cine-3 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
altman analysis of cardiological indices of left ventricular function ( mean    standard deviation ; n  =  6 healthy mice plus 5 mice with myocardial infarct ) measured from cine images acquired with threefold kt - blast acceleration ( ktb-3 ) compared with images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
altman plots of cardiological indices of left ventricular function [ n  =  6 healthy mice and 5 mice with myocardial infarct ( grey symbols ) ] , comparing measurements made from threefold kt - blast accelerated images ( ktb-3 ) and cine images acquired with one signal average ( cine-1 ) .
edv end diastolic volume , esv end systolic volume , sv stroke volume , ef ejection fraction , edm end diastolic mass , esm end systolic mass .
in this study , we implemented threefold kt - blast accelerated cardiac imaging in mice , comparing it with a single - average cine sequence and our standard three - average cine sequence .
initial simulations of kt - blast undersampling showed , as expected , that the numerical reconstruction error  increased with increasing simulated acceleration factor r. the error manifested itself as increased ghosting artefacts in the reconstructed images , which became more evident at r  =  4 and r  =  6 . difference images ( such as fig . 
estimates of edv remained acceptably accurate for acceleration factors up to 6 , whereas esv was increasingly overestimated , and hence ef and sv were underestimated .
possible reasons for the overestimation of esv include more flow artefacts during systole , the smaller heart dimensions than at edv making papillary muscles harder to define , and reconstruction artefacts taking up a greater proportion of the cardiac cross sectional areas . the errors for r  =  3 were considered acceptable in the context of reported intra- and inter - observer variabilities in the range 311  % [ 18 , 19 ] , and
hence this was the target acceleration factor for the subsequent implementation of kt - blast .
estimates of left ventricular mass ( edm and esm ) were relatively robust to the simulated acceleration factor .
the differences ( group biases ) in cardiological parameters between the standard and implemented accelerated acquisitions were of the order of 510  % , which are rather higher than the values of approximately 3  % found by jahnke et al .   for left ventricular volumes in a human study comparing standard and kt - blast techniques .
many of the reasons discussed above for estimation of esv may apply , together with the overall lower snr and cnr of small animal imaging compared with clinical imaging .
it might have been expected that true accelerated scans , with training data collected in a separate scan , would have performed worse than simulated versions for which all the data was collected in a single scan . however , no such systematic differences were evident .
parameter biases were generally smaller for the infarcted animals than the healthy animals . in part
this was due to the mouse that had the greatest ( negative ) bias for edv , esv and sv ( figs .  5 , 6 ) .
the reasons for this bias are not entirely clear . although the cine-1 images ( quality score 3 ) showed more motion ghosting artefacts than the cine-3 images ( quality score 4 ) , the corresponding kt - blast images were not so affected ( quality score also 4 ) .
the subjective image quality score q decreased as the simulated acceleration factor increased , as might be expected .
even for fully sampled k - space , the mean value was 4.22 rather than the theoretical maximum of 5 , because of poor quality images in two mice .
for the actual kt - blast scans , q was similar to ( although slightly higher than ) that for the simulated threefold acceleration .
q for the cine-1 scans was lower , especially for the healthy mice , reflecting the noisy appearance of the images .
measured cnr and q values were higher in the infarcted hearts than in the healthy hearts , a finding which we ascribe partly to the reduced motion , and correspondingly less motion artefacts , in the infarcted hearts . a simple measure of myocardial motion can be derived from the change in equivalent radius between edv and esv . when multiplied by heart - rate this in turns gives a measure of wall velocity . despite the slightly higher heart - rate of the mi group , the  wall velocity 
was significantly less than for the control animals ( 8.9    2.1 vs 12.7    1.3  mm / s ; p  =  0.01 ) , and may well have contributed to the higher image quality .
we used a 39  mm rf coil for imaging the healthy animals since we wanted to explore a wide range of body weights ( 2855  g ) . on the other hand ,
our method for generation of myocardial infarcts   is better suited to younger animals which had lower body weights ( 2230  g ) and for which we were able to use a 33  mm rf coil .
this may also have reduced the noise and hence contributed to increased cnr and q in the infarcted animals . since each animal was scanned in the same coil for all three techniques ( cine-3 , cine-1 and ktb3 ) , the comparisons are valid regardless of the exact coil used .
as improved coils become available , all the results should improve , but we would expect the relative merits of the three techniques to remain similar . acquiring images using the standard cine sequence but with only one signal average , and with the threefold accelerated kt - blast sequence allowed a direct comparison between these two approaches to reducing the standard scan time by a factor of three .
visually , acquiring only one average resulted in noisy images , whereas the threefold kt - blast acceleration resulted in images that appeared very similar to those acquired with the standard acquisition ( fig .  1 ) .
the kt - blast reconstruction uses a low - pass filter on the training data , and this promotes smoothness in the resulting images , thereby reducing noise effects at the expense of possible blurring of myocardial edges . despite their noisy appearance , cine-1 images gave results slightly nearer to the  gold standard  of cine-3 images than did the kt - blast accelerated images , except for esm in healthy mice and edm in infarcted mice .
apart from signal - to - noise considerations , a possible advantage of collecting multiple acquisitions in the presence of periodic and quasi - periodic motion is to reduce artefacts caused by occasional fluctuations in the cardiac or respiratory rates .
even when using dual gating with dummy excitation pulses during respiration so as to maintain the equilibrium magnetisation , fluctuations in rates , or incorrect triggering , will cause ghosting artefacts that can generally be reduced by multiple acquisitions .
hence for the same total scanning time , three signal averages with threefold undersampling of k - space might be expected to perform better than a single conventional acquisition in the presence of asynchronous effects . however , in this study , we found that there were no significant differences between the techniques in terms of manual measurement of cardiological indices .
the appearance of the cine-1 images could be improved by  kt - denoising  , that is , exploiting the denoising properties of the kt - blast algorithm even in the absence of acceleration .
the overall acceleration factor as implemented was actually 2.4  times when taking into account the acquisition of 16 rows of k - space  training  data .
it is possible that fewer rows would have sufficed , as reported by others , in which case an overall factor nearer to three could have been achieved .
we found no significant biases between cardiological indices derived from kt - blast or cine-1 scans compared with fully sampled scans for healthy mice or for mice with myocardial infarcts .
the method of k - space undersampling coupled with kt - blast reconstruction can be used with any rf coil setup , and does not require multiple independent receiver coils as does parallel imaging . undersampling schemes employing compressed sensing reconstruction   are also likely to prove useful in rodent studies , and although not specifically optimised for periodic data as is kt - blast , the achievable acceleration factors appear similar . future work should include direct comparisons .
acceleration factors so far reported using parallel imaging in rodent studies are up to four for rats using a four - element coil array   and three for mice using an eight - element coil .
the combination of parallel imaging and k - space undersampling techniques is expected to lead to further reduction in scanning times , thus improving animal welfare and increasing throughput .
due to use of quadrature coils in the present work , parallel imaging could not be explored or combined with the investigated approach .
acceleration will ultimately be limited by the snr achievable in rodent imaging studies . for large - scale imaging studies
an alternative way of increasing throughput is to scan multiple animals simultaneously . providing that the difficulties of handling a number of animals simultaneously can be overcome , this method can lead to a significant reduction in the time taken to run a complete study , but does not benefit individual animals .
simulations and actual implementation showed that standard cardiological indices in mice can be determined with acceptable accuracy for modest acceleration factors . in this pilot study , running the standard cine sequence with only one average gave slightly ( though not significantly ) better results ( i.e. , lower biases ) than using threefold kt - blast acceleration , even though the image quality was subjectively better for kt - blast acceleration .
we have therefore demonstrated that accelerated cardiac imaging of mice is feasible , enabling significant reduction in imaging times .
 objectwe evaluated the use of kt - broad - use linear acquisition speed - up technique ( kt - blast ) acceleration of mouse cardiac imaging in order to reduce scan times , thereby minimising physiological variation and improving animal welfare . 
 
 materials and methodsconventional cine cardiac mri data acquired from healthy mice ( n  =  9 ) were subsampled to simulate kt - blast acceleration . 
 cardiological indices ( left ventricular volume , ejection fraction and mass ) were determined as a function of acceleration factor . 
 kt - blast threefold undersampling was implemented on the scanner and applied to a second group of mice ( n  =  6 healthy plus 6 with myocardial infarct ) , being compared with standard cine imaging ( 3 signal averages ) and cine imaging with one signal average.resultsin the simulations , sufficient accuracy was achieved for undersampling factors up to three . 
 cardiological indices determined from the implemented kt - blast scanning showed no significant differences compared with the values determined from the standard sequence , and neither did indices derived from the cine scan with only one signal average despite its lower signal - to - noise ratio . 
 both techniques were applied successfully in the infarcted hearts.conclusionfor cardiac imaging of mice , threefold undersampling of kt - space , or a similar reduction in the number of signal averages , are both feasible with subsequent reduction in imaging time . 
Introduction
Materials and methods
Simulated undersampling
Accelerated acquisition
Results
Simulated undersampling
Accelerated acquisition
Discussion
Conclusion