Ten subjects (9 males, 1 female ) originally referred for evaluation of myocardial ischemia under stress but with no signs or symptoms of mesenteric ischemia, and normal myocardial perfusion studies, were examined using TurboFLASH MRI during bolus injection of Gd-DTPA . The mean age was 57.2 years (range 31-77 yr. ) with a mean weight of 81.1 kg (range 60-125 kg). The described protocol was submitted and approved by the institutional review board committee at our institution. Criteria for inclusion in the study included: 1) the ability to safely undergo pharmacologic stress, 2) no unstable angina, 3) no contra-indication to MR imaging, and 4) the ability to give informed consent. Informed consent was obtained after the procedure was fully discussed with each subject. Each subject abstained from any substances containing xanthines for 48 hr and fasted for 8 hr. Vital signs and ECG were obtained prior to the examination and ECG leads were placed on the back. All subjects were imaged on a Siemens Magnetom 1.0T unit (Siemens Medical Systems, Iselin, NJ) in a supine position using the vendor supplied body coil. Preliminary resting MR images were obtained during the administration of 0.04 mmol/kg gadopentate dimeglumine (Gd-DTPA, Magnevist, Berlex, Montvale, NJ.). No subject suffered complications from the examination, and none required premature aminophylline reversal, but 100 mg aminophylline IV was administered routinely after all studies were completed. Of the ten subjects examined 3 were diabetic. 1 subject (male, 60 yrs old) with known mesenteric ischemia (stenosis at origin of SMA) was also examined as a representative case to evaluate for differences in response to DP stress compared to the control group. Though the control group does not constitute a totally normal population, it is a group of similar subjects for preliminary data on organ perfusion.

The fast imaging method used in this study relies on a gradient echo sequence with a very fast repetition time (TR) and a reduced number of phase encoding steps. A short echo time (TE) minimizes signal loss due to local magnetic field inhomogeneities (T2* effects) and flow-related dephasing. To emphasize T1 contrast, the data acquisition interval is prefaced with a 180° inversion pulse. Because the total time for data acquisition is short relative to the T1 of the liver and spleen at 1.0T, tissue contrast is similar to a standard inversion-recovery sequence with an infinite TR. The inversion time (TI) was selected to obtain the greatest nulling of the signal from nonenhanced liver and spleen.

During contrast administration organs perfused by Gd-DTPA will produce nonzero signal. Low flip angle ECG gated MR imaging with predominantly Tl-weighted imaging parameters performed 10 to 45 and up to 90 seconds after rapid bolus injection of Gd-DTPA with images every 3-4 seconds, each within a breathhold, similar to the technique reported by van Rugge [₃], with the Turbo-FLASH technique was the basic acquisition technique [₄] using a double oblique angulation to image the liver, spleen, stomach and left ventricle was used so that intravascular and parenchymal enhancement could be measured. Twenty minutes later (to allow dominant clearance of most of the Gd-DTPA) the subject was administered 0.56 mg/kg of Dipyridamole over a 4 min period under constant physician supervision with ECG , blood pressure, and pulse monitoring using a Marshal TM94 digital BP monitor (Omron Health, Vermont Hills, IL) and oxygen saturation measurements with an 4500 MRI Pulse oximeter (In-vivo medical instruments, Winter Park, FL). Two minutes later an additional 0.04 mmol/kg gadopentate dimeglumine (Magnevist, Berlex, Montvale, NJ.) was given by bolus technique. Stress MRI images were therein obtained with the same technique and angulation.

TurboFLASH images were obtained with a double oblique method [8]. Imaging parameters included a bandwidth of 350 Hz/pixel, a repetition time (TR) of 12 msec, and an echo time (TE) of 6 msec. The flip angle was 12°. A. Representative image is demonstrated in figure 1. An inversion time of 100 msec was selected. Since the mean of hepatic and splenic T1 relaxation time at 1.0 T is approximately 500 msec[₅,₆], the null point thus calculates to 333 msec. Because the net imaging time was 380 msec, the central views in k space, were acquired at 290 msec (100+(380/2)), within the theoretical null point for the mean value of these organs. The images obtained were 10 mm thick and 64 X 128 interpolated to 256 x 256 with a 35-cm field of view (FOV). After the intravenous bolus of 0.04 mmol/kg of gadopentate dimeglumine, imaging was begun immediately so that 20-30 images were obtained at the same level every 3-4 seconds with voxel size of 1.37 x 1.37 x 10 mm. All images were prospectively triggered from the R wave of the cardiac cycle, and all were obtained within 380 msec during the R-R interval. The subjects were instructed to breathe quietly and to stop breathing during each brief acquisition which provided reproducible slice positioning. A relationship between signal intensity and contrast concentration [₇] and thus perfusion has been shown by others using similar MR techniques [₈].

Figure 1

Figure 1: Representative double oblique image including liver, spleen, stomach (arrow), and right and left ventricular chambers

Figure 2

Figure 2: Representative sequential images of the liver during Gd-DTPA administration

Images were transferred onto a Macintosh Quadra 950 (Apple, Cupertino CA) with analysis performed using the NIH Image V.1.49 (NIH, Bethesda MD) program. Signal intensity was measured with an operator-adjustable circular region of interest, which was set at 30 pixels for the pectoral muscle, left hepatic lobe, and spleen. Gastric wall enhancement was measured using a curved line of 30 pixels along the fundus, enhancement of the splenic flexure of the colon was measured using a circular ROI encompassing the flexure and its contents. Once the ROI was placed for a particular measurement on the baseline image, it was kept constant in position and size with respect to the organ position with adjustments made to compensate for respiratory induced organ motion within the field of view for the subsequent images. All signal-intensity measurements on MR images were standardized to (divided by) the signal intensity of the epicardial fat (which was chosen due to its location within the magnetic isocenter) ; and logarithmic scaling was calculated by -Log (SI(t)/SI(0)) (representative curves are shown in figure 1). Note that SI(0) is the standardized value of signal intensity before gadolinium administration. The linearity of this transformation for the dose and imaging protocol used has been established when evaluating cardiac output elsewhere [8]. Analysis of plateau signal enhancement of each organ was then performed using Microsoft Excel V4.0 (Microsoft, WA) and student’s T-test was used to calculate significance [₉] , the rise portion of the time-signal curves was analyzed using linear regression and Chow’s analysis [₁₀] and comparison between all organs and within each organ before and after stress was performed. The quality of the timing of the study was rated by observing the timing of the intravascular enhancement within the left ventricular chamber, with peak enhancement occurring within 30 seconds of injection.

Though all had a measurable response to DP with depression of blood pressure, none had a depression of blood pressure requiring clinical intervention. There was compensatory elevation of heart rate during stress with the heart rate (HR) -mean arterial pressure (MAP) product stable over the imaging period. The HR*MAP product was normalized by dividing by the baseline HR*MAP product before initiation of stress over the first 10 minutes remained at 0.95±0.08, indicating essentially no change in cardiac function or net output, corroborating previous measures of cardiac output during Dipyridamole stress [5,8,₁₁]. None of the patients had any known or documentable liver disease based on biochemistry and scout MRI images

Analysis of intravascular enhancement demonstrated that peak left ventricular enhancement occurred within 30 sec (range: 20-30 sec) of Gd-DTPA administration and that less than 10% residual signal enhancement was present in all subjects prior to administration of the second bolus of Gd-DTPA, based on first scan just prior to second injection. Normalizing with respect to the resting muscle perfusion (defined as 1) the plateau relative perfusion values are demonstrated in table 1. The pectoral muscle perfusion was chosen for normalization due to its non-significant enhancement during the bolus Gd-DTPA injection. Each patient signal analysis was performed and percentages calculated on an individual basis with statistical analysis performed on the group as a whole. The effects of changing inversion time between patients were not specifically investigated but signal nulling appeared consistent between patients.

Table 1: Relative perfusion before and after Dipyridamole administration where 1.0 is defined as resting perfusion of pectoral muscle at rest. Value in parentheses represents increase rather than decrease in perfusion.

Normal subjects (n=10)

Figure 3

In subject with mesenteric ischemia

Figure 4

Note * indicates P<0.01 with respect to similar parameter in ’normal cohort’. This demonstrates the difference in response to DP in the control group and the subject with mesenteric ischemia. Since pectoral muscle perfusion is defined as the baseline, the relative lack of change in perfusion in the ischemia subject may be due to lack of statistical power to detect a physiologic change.

First pass analysis after Dipyridamole of liver, stomach and splenic perfusion demonstrated rapid enhancement while the pectoral muscle demonstrated minimal enhancement. This was reproducible among all 10 subjects with normalized perfusion values consistent and distinctly different among each organ during the resting state. Performing linear regression on the normalized signal during the rapid intravascular phase, demonstrated statistically significant difference in organ perfusion (P<0.01), with statistically significant depression of liver and splenic perfusion by 61% (P<0.01) and 35% (P<0.01)respectively with a decrease in gastric perfusion by 74% (P<0.01) by paired T-test and Chow’s Test for difference between sets of coefficients in linear regressions [10]. These relative changes are shown in table 1. In the subject with mesenteric ischemia the celiac axis changes were comparable however, while in the normal subjects there was effective shunting from the celiac axis to the splenic flexure of the colon, in the subject with mesenteric ischemia there was discordant diminution of perfusion to the colon as shown in table 1.