Toward necrotic cell fraction measurement by contrast-enhanced MRI of reperfused ischemically injured myocardium.
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Publications and source records attributed to M Saeed.
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RATIONALE AND OBJECTIVES: The authors used gadolinium (Gd) chelate as a T1, T2, and T2* enhancing agent in reperfused myocardial infarction to compare the appearance of reperfused myocardial infarction on spin echo and gradient echo magnetic resonance (MR) sequences. METHODS: Rats (n = 28) were subjected to reperfused myocardial infarction and received no contrast medium, 0.2, 0.5, or 1.0 mmol/kg Gd DTPA-BMA. Spin echo and gradient echo MR images of the excised hearts (n = 7 rats per group) were acquired using 2.0 T system: repetition time (TR)/echo time (TE) = 300/20 ms for T1-weighted spin echo, TR/TE = 4000/80 ms for T2-weighted spin echo, and TR/TE = 600/10, 15, 20, and 30 ms for gradient echo imaging. Regional T2 and T2* relaxation times were measured. Triphenyl tetrazolium chloride was used to verify regional infarction. RESULTS: Unenhanced spin echo images failed to distinguish infarcted from normal myocardium. On Gd DTPA-BMA enhanced T1-weighted spin echo images, infarction was depicted as a high-intensity region "hot spot." On the other hand, the infarcted region was visualized as a low-signal region "cold spot" on Gd DTPA-BMA enhanced T2-weighted images. Changes in signal intensity and T2 relaxation time on T2 weighted images were dose dependent. On gradient recalled echo images, the infarcted region was discriminated from normal myocardium by a dark boundary zone, which was visible only at 1.0 mmol/kg. The presence of infarction was documented in every heart. CONCLUSIONS: The contrast between normal and infarcted myocardium was affected greatly by the dose and imaging parameters. The results indicate that spin echo and gradient echo images have greatly differing sensitivities to extracellular gadolinium chelates. Changes in myocardial T2 relaxation time, but not T2*, correlated well with the dose.
PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for detecting tumor necrosis in an animal model of osteogenic sarcoma. MATERIALS AND METHODS: Twelve rats with osteogenic sarcoma underwent T1-weighted unenhanced and gadolinium-enhanced spin-echo and diffusion-weighted spin-echo MR imaging. Histologic correlation was performed. Signal intensities, T2 relaxation times, normalized apparent diffusion coefficients, and relative signal intensity increases were calculated. RESULTS: On diffusion-weighted images, necrotic tumor showed low signal intensity (mean normalized apparent diffusion coefficient, 0.46 +/- 0.20 [1 standard deviation]), indicating rapid diffusion of water molecules as a result of loss of membrane integrity, while viable tumor showed high signal intensity (mean normalized apparent diffusion coefficient, 0.16 +/- 0.05; P < .0001). Differences in the T2 relaxation times and relative signal intensity increases between viable and necrotic tumor were not statistically significant. CONCLUSION: Normalized apparent diffusion coefficients are more accurate in differentiating between viable and necrotic tumor than are T2 relaxation times or relative signal intensity increases on contrast-enhanced images. Signal intensity overlap between viable and necrotic tumor on gadolinium-enhanced images may be caused by the small molecular size of the agent, which permeates the interstitial space freely, thereby also enhancing necrosis. Diffusion-weighted MR imaging depicts differences in diffusion and, ultimately, in membrane integrity between viable and necrotic tumor and may be used to monitor tumor viability during treatment.
A rapid and automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast enhanced MR imaging was developed and tested in disease models of cancer, inflammation, and myocardial reperfusion injury. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium (MMCM) designed for blood pool enhancement. Maps of PS and BV in disease models of adenocarcinoma, intramuscular abscess inflammation, and myocardial reperfusion injury clearly depicted zones of increased permeability (up to approximately 500 microl/cc/h--compared to <25 microl/cc/h in normal tissues). As revealed on PS maps, the rank ordering of studied permeability abnormalities was reperfusion injury > inflammation > tumors. A rapid, automated mapping technique derived from dynamic contrast-enhanced MRI data can be used to facilitate the identification and characterization of pathophysiologic abnormalities, specifically relative increases in blood volume and/or microvascular permeability.
This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). delta R1 was repeatedly measured over 30 min. Gd-BOPTA caused greater delta R1 for blood and myocardium than did Gd-DTPA; clearance of both agents from normal- and infarcted myocardium was similar to blood clearance; plots of delta R1 myocardium/delta R1 blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTPA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater delta R1 than Gd-DTPA in regions which contain serum albumin.
OBJECTIVES: This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns. BACKGROUND: Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity). METHODS: To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesla system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing. RESULTS: Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA-enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/ normal myocardium increased with increasing duration of ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin-enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (overall p value < 0.0001, ANOVA). CONCLUSIONS: At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.
OBJECTIVE: To compare transurethral electrovaporization of the prostate (TUVP) with conventional transurethral resection of the prostate (TURP) in the treatment of men with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Seventy consecutive patients with symptomatic BPH and a prostate size of < 60 g were prospectively randomized between equal treatment groups; one group underwent standard TURP and the other TUVP. Patients were assessed at baseline and 1, 3, 6 and 12 months after treatment, giving a mean (SD) duration of follow-up of 14.4 (1.9) months (range 12-17). Variables evaluated included the duration of operation, catheterization and hospital stay, and changes in blood levels of haemoglobin, haematocrit and sodium 1 h after the operation. The American Urologic Association (AUA)-7 symptom score, peak urinary flow rate (Qmax), post-voiding residual urine volume (PVR) and sexual function were also evaluated during the follow-up. RESULTS: Patients of both groups were balanced for the different baseline variables. The mean (SD) operative duration of TUVP was 52 (12.5) min, significantly longer than that of TURP, at 39.7 (8.8) min (P < 0.001). One hour after TURP, patients had significantly lower levels of haemoglobin, haematocrit and Na. The mean (SD) duration of catheterization after TURP was 2 (0.8) days, significantly more than after TUVP, at 1.1 (0.4) days (P < 0.001). The mean (SD) hospital stay was 2.5 (1) days after TURP and 1.5 (0.7) after TUVP (P < 0.001). Compared with baseline values, the AUA-7 symptom score, Qmax and PVR improved significantly in both groups at all intervals of follow-up and there were no significant differences between the groups during the follow-up. None of 15 potent men undergoing TURP and two of 18 potent men undergoing TUVP complained of impotence during the follow-up. CONCLUSIONS: TUVP is as effective as TURP in the treatment of BPH in men with a prostate size of < 60 g. TUVP has the advantages of less blood loss, less absorption of irrigant and a shorter hospital stay, but it had a significantly longer operative duration.
PURPOSE: Considerable clinical interest has focused on the size of ischemic myocardium. Fast MR imaging in conjunction with MR contrast media has the potential to identify hypoperfused and infarcted myocardium. This study used MR perfusion imaging to detect and quantify reperfused ischemic myocardium during a brief coronary occlusion and reperfusion, and to characterize the spatial extent of ischemic and reperfused ischemic myocardium relative to the "true" size of the area at risk as defined in histochemical morphometry at post mortem. MATERIAL AND METHODS: The left circumflex (LCX) coronary artery in 8 dogs was occluded for 15 min followed by reperfusion in order to produce regional reversible myocardial ischemia. Perivascular Doppler probes were used to measure blood flow in the left anterior descending (LAD) and LCX coronary arteries. Fast inversion recovery-prepared gradient-recalled-echo images were acquired to delineate the ischemic area during occlusion, and the area of reversible ischemic injury at 1 and 30 min of reperfusion. The size of ischemic and reperfused ischemic myocardium were compared with the area at risk as determined by histochemical morphometry at post mortem. RESULTS: During LCX occlusion, LCX flow decreased from 16+/-1 to 0.2+/-0.1 ml/min. On contrast-enhanced images, ischemic myocardium was evident as a zone of relatively low signal intensity (SI) compared to normal myocardium. The size of the ischemic region was significantly smaller (30+/-2%) than at post mortem (36+/-3%; p<0.05). Immediately after reperfusion, LCX flow increased to 83+/-11 ml/min and the contrast medium caused greater enhancement in the reperfused ischemic region than in the normal myocardium (69+/-3 vs 42+/-3 arbitrary units; p<0.05). The increase in regional SI correlated closely with the increase in regional blood flow (r=0.73). At 1 min of reperfusion, the size of the reperfused ischemic myocardium was larger (48+/-3%, p<0.05) than the area at risk measured at post mortem. At 30 min of reperfusion, when the flow returned to baseline values (16+/-2 ml/min), contrast bolus produced no differential enhancement between the 2 myocardial territories. CONCLUSION: MR perfusion imaging has the potential to detect and quantify the size of ischemic myocardium and the region of post-occlusive hyperemia in the early reperfusion period. There is a significant direct linear relationship between the regional contrast enhancement of reperfused ischemic myocardium and the blood flow during post-occlusive hyperemia. The difference in the size of the area at risk at MR perfusion imaging and at histochemical morphometry may reflect an influence of coronary collateral circulation.
OBJECTIVE: Breath-hold velocity-encoded cine (VENC) MR imaging has been proposed as a method for measuring coronary blood flow. However, most studies have measured velocity rather than volume flow rate in the coronary arteries. The purpose of this study was to measure volume flow rate in the coronary artery of dogs using high-speed gradients and to compare MR flow measurements with those obtained with a sonographic flowmeter. MATERIALS AND METHODS: Fast VENC MR images were obtained with a high-speed-gradient 1.5-T MR system in seven anesthetized dogs before and after administration of dipyridamole. Images were acquired on double oblique planes perpendicular to the left anterior descending arteries with a slice thickness of 5 mm, a field of view of 20 x 10 cm, a velocity window of +/- 1 m/sec, an average imaging time of 21 sec, a TR/TE of 11/5, and a temporal resolution of 44 msec. RESULTS: Coronary flow measured with VENC MR imaging correlated well with flow measured by the flowmeter (r = .95, slope = 0.97, n = 88). Interobserver variability in measuring coronary flow volume was 8%. CONCLUSION: Fast VENC MR imaging with high-speed gradients can provide accurate quantification of volume flow rate in coronary arteries.
Fast magnetic resonance (MR) imaging techniques have the capability of demonstrating regions of ischemia caused by stenosis. The size of the potentially ischemic area determines the importance of the stenosis. The purpose of this study was to determine the relative values of relaxivity-enhancing and magnetic-susceptibility MR contrast media in detecting and sizing the area at risk in dogs. Eight dogs were subjected to critical left circumflex coronary artery (LCX) stenosis. Sixty sequential inversion-recovery- and driven-equilibrium-prepared fast gradient recalled echo images were acquired during bolus administration of 0.03 mmol/kg gadodiamide or 0.4 mmol/kg sprodiamide in basal and vasodilated (dipyridamole-stress) states. The size of the area at risk was measured and compared with that measured post mortem. In the basal state, gadodiamide and sprodiamide equivalently altered the signal intensities of nonischemic myocardium and the territory of stenosed coronary artery. Dipyridamole produced a significant increase in left anterior descending coronary artery flow with a decrease in LCX flow. The hypoperfused region was observed as a low-and high-signal intensity region after administration of gadodiamide and sprodiamide, respectively. The size of the hypoperfused region was slightly smaller with gadodiamide (37.4% +/- 2.8%) and sprodiamide (34.0% +/- 2.2%) than the true area at risk measured post mortem (41.8% +/- 2.2%; p < 0.05). Dipyridamole perfusion MR imaging with relaxivity or susceptibility contrast media is a noninvasive method to identify and quantify the area at risk in the territory of a stenotic coronary artery. Changes in myocardial signal intensity on fast gradient recalled echo images reflect the augmentation of flow and volume induced with dipyridamole and are consistent with the "steal phenomenon."
Contrast-enhanced magnetic resonance (MR) imaging was used to detect and quantify the extent of myocardial injury after a brief coronary occlusion and reperfusion in response to verapamil treatment in a rat model of left ventricular hypertrophy (LVH). Two groups of rats were prepared by banding the abdominal aorta for 7 to 8 weeks to produce LVH. Group 1 (n = 13) received oral verapamil for 3 days, whereas group 2 (n = 13) received no therapy. Before MR examination was performed, each rat was subjected to 25 min of coronary artery occlusion followed by 1 hour of reperfusion. T1-weighted spin echo images were acquired before and after 0.3 mmol/kg gadoteridol was injected. Three images were acquired at contiguous levels of the LV and used to estimate the size of the myocardial injury. The size of the infarcted region was demarcated at postmortem examination by using triphenyltetrazolium chloride dye (TTC). Before contrast medium was administered, no significant difference in signal intensity was seen between nonischemic and reperfused ischemically injured myocardium. After gadoteridol was injected, a hyperintense zone indicative of myocardial injury was observed in 8 of 13 rats treated with verapamil and in all untreated animals. The size of the injury was significantly larger in untreated hearts than in hearts treated with verapamil as defined on MR images (25% +/- 5% vs 18% +/- 5%, p < 0.05) and TTC staining (12% +/- 4% and 4% +/- 1%, p < 0.05). Good correlation (r = 0.91) was found between the two measurements. No significant difference in the size of jeopardy area was seen between the two groups as (defined by blue dye infusion). In conclusion, contrast-enhanced MR imaging is a suitable technique to evaluate the effects of therapies applied to reduce myocardial injury. Verapamil can cause reduction in the extent of ischemic injury after reperfusion of hypertrophied myocardium.
RATIONALE AND OBJECTIVES: We evaluated and compared the acute cardiovascular effects of equiosmolar doses of recently developed nonionic monomer and macrocyclic dimer magnetic resonance (MR) imaging contrast media with the clinically available ionic and nonionic MR contrast media. METHODS: Normotensive adult Sprague-Dawley rats were divided into six groups of seven rats per group. Group 1 received the nonionic monomer Gd-CMPA-BMPA (500 mmol/l solution); group 2 received the nonionic dimer Gd(2)2(O)DO3A (500 mmol/l solution); group 3 also received Gd(2)2(O)DO3A but at a higher concentration (1,000 mmol/l solution); group 4 received gadopentetate dimeglumine (500 mmol/l solution); and group 5 received gadodiamide (500 mmol/l solution). Each rat received a rapid (1-2 sec) bolus intravenous injection of 0.1, 0.25, and 0.5 mmol/kg of each contrast agent. Group 6 was used to test the peak effects of quiosmolar glucose solutions (500, 1,000, and 2,000 mOsm/kg water). Data were acquired at baseline, 20 sec (peak effect) after injection, and 1, 3, 5, and 10 min after injection. Peripheral (systolic, diastolic, and mean) pressure, central venous pressure, left ventricular (LV) pressure (peak systolic and end diastolic) pressure, first derivative of left ventricular pressure (+/-dP/dt), rate pressure product, and heart rate were measured. RESULTS: Bolus administration (0.1, 0.25, and 0.5 mmol/kg) of Gd-CMPA-BMPA and gadodiamide (500 mmol/l) had no significant effects on the monitored cardiovascular parameters. Bolus injection of 0.25 and 0.5 mmol/kg Gd(2)2(O)DO3A (500 and 1,000 mmol/l) and gadopentetate dimeglumine (500 mmol/l) caused transient cardiovascular depression, including decreased peripheral blood pressure, LV systolic pressure, peak positive and negative dP/dt, and rate pressure product, but an increased LV end diastolic pressure. These cardiovascular effects were slightly less profound than those produced by gadopentetate dimeglumine. CONCLUSION: Gd-CMPA-BMPA and gadodiamide have no adverse cardiovascular effects. Gd(2)2(O)DO3A and gadopentetate dimeglumine cause vasodilation and reduced cardiac performance. Therefore, presuming similar effects, if Gd(2)2(O)DO3A and gadopentetate dimeglumine are to be used at high doses for the MR quantification of blood volume or as a bolus for perfusion study, appropriate consideration should be given to possible adverse physiologic changes.
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Recent developments in MR imaging have opened up new avenues in the investigation of ischaemic heart disease. Conventional unenhanced spin-echo sequences have been used to detect and quantify myocardial infarction. Along with the technical advances aimed at reducing motion artifacts and imaging time, the advent of contrast media for MR imaging has further strengthened its diagnostic capacities. The applications of MR contrast media are increasing, and they are becoming more specific, to enable differentiation of occlusive and reperfused myocardial infarctions and to discriminate between reversible and irreversible myocardial injury. Previous studies have also indicated that dual administration of both relativity-based and susceptibility-based contrast media can be used to determine whether viable myocardium is present in the reperfused ischaemic area. Magnetic susceptibility MR contrast media have the potential to demonstrate a region of the ischaemically injured myocardium in which myocardial necrosis is present. A cornerstone in the MR assessment of ischaemic heart disease has been achieved with the advent of fast MR imaging techniques. Ultrafast gradient-recalled-echo sequences or echo-planar imaging allow to monitor the first passage of the contrast medium through the heart. With the aid of MR contrast media, these techniques may be useful in estimating regional myocardial perfusion and blood volume. Experimental and clinical perfusion studies indicate that perfusion-sensitive MR imaging, particularly in concert with coronary vasodilators, can detect compromised myocardium. Combining myocardial perfusion imaging with the anatomic and functional information provided by other MR imaging techniques such as cine and velocity-encoded sequences could make MR imaging a comprehensive noninvasive diagnostic tool for the assessment of ischaemic heart disease.
Atrial fibrillation (AF) was induced electrically and the duration of AF was measured in six isoflurane-anesthetized sheep (weight range 54.5-72.7 kg), and in five unanesthetized sheep (weight range 60-75 kg). In the anesthetized sheep, AF was induced by direct electrical stimulation of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostigmine (10 micrograms/kg IV) was administered and the duration of AF was again measured. Then cholinergic drive was increased by bilateral electrical vagal stimulation; AF was induced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF lasted 10 seconds, 11% lasted 20 seconds, and only 1% lasted 200 seconds. However, in one anesthetized animal AF was sustained for 4,800 seconds with no drug or vagal support. The administration of neostigmine alone in 3 anesthetized animals more than doubled the average duration of AF. In the animals with vagal stimulation (after neostigmine), AF persisted throughout stimulation, but ceased shortly after vagal stimulation was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequency ranged from 325-750/min. The unanesthetized sheep were lightly sedated with a small dose (200 micrograms/kg IM) of xylazine to make them less sensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 micrograms/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60-2,000 micrograms of phenylephrine. AF was electrically induced at the time of maximum reflex slowing in heart rate. For the control (no drug) studies, 64% of the AF episodes lasted 10 seconds, 20% lasted 20 seconds, and only 2% of the episodes lasted as long as 140 seconds. When phenylephrine was injected after neostigmine to provide increased cholinergic drive, the duration of fibrillation depended on the dose of phenylephrine. In a 60-kg sheep, the duration of AF increased from 1 second with an intravenous dose of 60 micrograms to 700 seconds with an intravenous dose of 2,000 micrograms. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by the intravenous phenylephrine; for example a single intravenous 500-micrograms dose produced AF ranging from 190-540 seconds among the sheep. The duration of AF was most controllable in the anesthetized sheep, following neostigmine administration and with bilateral vagal stimulation. In the unanesthetized sheep, AF could generally be sustained for more than the duration of the half-life (about 4 minutes) of phenylephrine following neostigmine. However, there was a large variation in the duration of AF among the animals for the same dose of phenylephrine. This study identifies two methods (direct vagal stimulation and reflex vagal stimulation) for providing the cholinergic drive needed to sustain AF in the adult sheep. The duration of AF is sufficiently long to enable the measurement of electrical atrial defibrillation threshold.