Synopsis
We
tried to develop and validate an early detection technique of chemo therapy
cardiotoxicity in the cancer treatment using cardiovascular magnetic resonance
imaging. We hypothesized myocardial blood flow (MBF), more sensitive
technique than EF or DHE, provides information on the altered physiology and
function conditions of the heart. Chemo treatment induces changes in myocardial
perfusion at rest enough to be detected with model based quantitation, with
sequential imaging on the same subject. It provides an earlier indication of
cardiotoxicity.
Myocardial flow is closely associated with cardiac
function1. However, it is unclear how the perfusion changes at the tissue level
in response to hemodynamic alteration, such as in patients undergo chemo
therapies. In this study we sought to investigate the relationship of myocardial
resting perfusion in patients in chemo therapy versus those of age matching
normals using quantitative contrast 1st pass perfusion by MRI.
Cardiac function and regional myocardial resting dual bolus perfusion images were analyzed in 5 age-matching normal subjects (age: 57.2±5.5) and 6 patients (age: 55.7±14.8) who underwent chemo on a 1.5 T MRI scanner. The study was approved by the hospital IRB and written consents were collected from all subjects.
Breath holding first-pass perfusion studies were performed at
rest on a 1.5 T Siemens Sonata or Avanto scanner (Siemens Medical Solutions,
Malvern, PA), with a CP body array flex coil. After scout and cine LV
functional imaging, perfusion imaging was obtained with data acquisition
starting two cardiac cycles prior to administration of contrast agent.
Gadodiamide (Omniscan, Amersham Health Inc., Princeton, NJ) was injected first
at a dose of 0.005 mmol/kg (diluted to maintain the same volume as the standard
dose), then at a dose of 0.05 mmol/kg bodyweight, followed immediately by a
15-20 cc saline flush on both injections. Perfusion imaging was performed using
a partial Fourier saturation recovery steady state free precession (SSFP)
sequence to acquire 4 slices per heartbeat over 50 heartbeats for an imaging
time of 160 ms per slice. One short axis slice at mid ventricle and three
rotational long axis slices (as horizontal long axis (HLA), vertical long axis
(VLA), and left ventricular outflow tract (LVOT) views of the left ventricle,
all perpendicular to a left ventricular short axis) were prescribed. The
typical parameters were as follows: TR/TE/TI/FA = 2.9ms/1.3ms/90ms/50°, data
matrix 90×192, and voxel size 1.9×2.8×8 mm3. All image acquisition was ECG
triggered, and the non slice-selective 90° saturation pulses for each slice.
Using MASS (Medis, Leiden, the Netherlands) software, the
myocardial contours were manually drawn on an image showing good contrast and
then automatically propagated to each time point. The myocardium were divided
clockwise into 6 equal segments and the mean signal intensities of all pixels
in each myocardial segment at every time point were recorded. A custom
developed program read the segmental signal intensity saved from MASS and calculated
absolute perfusion according to the quantitative method using Fermi model as
deconvolution technique. Myocardial
perfusion was determined as the average of all 24 regions for each subject and 2
tailed student t-test was used for statistical analysis.
The patients all have normal ejection fraction (LVEF was 54.3±5.4%). The myocardial perfusion was significantly lower in patients 0.51±0.16 ml/min/g vs 0.77±0.24 ml/min/g in the age matching normals (p<0.05), as shown in Fig 1.
Reduced myocardial resting perfusion was associated with patients underwent chemo therapy even when their LVEFs are normal. Further studies are needed to fully understand the etiology of this change. This technique may potentially provide an early indication of cardiotoxicity.
Acknowledgements
The author thanks Haoyi Zheng,
MD for his efforts in recruit clinical patients.
References
1. Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross
CP. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab
therapy for breast cancer. J Am Coll Cardiol 2012;60(24):2504-2512.