Embozene™ microspheres induced nonreperfused myocardial infarction in an experimental swine model.

OBJECTIVES: To develop a magnetic resonance imaging (MRI) compatible, percutaneous technique for the generation of nonreperfused myocardial infarct (MI). BACKGROUND: Modeling nontreated MI has major importance in the development and preclinical testing of new therapeutic strategies for patients missing the time window suitable for revascularization following MI. METHODS: In 31 male swine, nonreperfused MI was generated by permanent occlusion of either the LAD or LCX coronary artery using 900 µm Embozene™ microspheres. Animals were monitored for 90 min postocclusion. Surviving animals were followed up for 2 (n = 6), 4 (n = 6), 14 (n = 6), or 56 (n = 6) days. At the end of the planned study session, contrast enhanced MRI, triphenyl-tetrazolium-chloride staining, and microscopic histopathology were carried out. RESULTS: The mortality rate in this study was 22.6%. Intraoperative arrhythmias occurred in 14 cases: premature ventricular complexes with (5) or without (3) ventricular tachycardia, 2nd degree atrio-ventricular block (1), and ventricular fibrillation (6). MRI, TTC, and histology confirmed the existence of MI in every case. Macroscopic pathology showed that the microspheres caused a practically total occlusion at the epicardial level of the coronary artery. Multiple infarcts were detected in one case, probably due to unintentional reflux of the microspheres. Microspheres retained in the coronary arteries did not cause any MRI artifact. CONCLUSIONS: The generation of nonreperfused MI is feasible by percutaneous injection of Embozene into the coronary artery system. The MI model thus obtained is suitable for the purposes of MRI experiments.

Percent infarct mapping for delayed contrast enhancement magnetic resonance imaging to quantify myocardial viability by Gd(DTPA).

PURPOSE: To demonstrate the advantages of signal intensity percent-infarct-mapping (SI-PIM) using the standard delayed enhancement (DE) acquisition in assessing viability following myocardial infarction (MI). SI-PIM quantifies MI density with a voxel-by-voxel resolution in clinically used DE images. MATERIALS AND METHODS: In canines (n= 6), 96 hours after reperfused MI and administration of 0.2 mmol/kg Gd(DTPA), ex vivo DE images were acquired and SI-PIMs calculated. SI-PIM data were compared with data from DE images analyzed with several thresholding levels using SI(remote+2SD), SI(remote+6SD), SI full width half maximum (SI(FWHM)), and with triphenyl-tetrazolium-chloride (TTC) staining. SI-PIM was also compared to R1 percent infarct mapping (R1-PIM). RESULTS: Left ventricular infarct volumes (IV) in DE images, IV(SIremote+2SD) and IV(SIremote+6SD), overestimated (P < 0.05) TTC by medians of 13.21 mL [10.2; 15.2] and 6.2 mL [3.79; 8.23], respectively. SI(FWHM), SI-PIM, and R1-PIM, however, only nonsignificantly underestimated TTC, by medians of -0.10 mL [-0.12, -0.06], -0.86 mL [-1.04; 1.54], and -1.30 mL [-4.99; -0.29], respectively. The infarct-involved voxel volume (IIVV) of SI-PIM, 32.4 mL [21.2, 46.3] is higher (P < 0.01) than IIVVs of SI(FWHM) 8.3 mL [3.79, 19.0]. SI-PIM(FWHM), however, underestimates TTC (-5.74 mL [-11.89; -2.52] (P < 0.01)). Thus, SI-PIM outperforms SI(FWHM) because larger IIVVs are obtained, and thus PIs both in the rim and the core of the infarcted tissue are characterized, in contradistinction from DE-SI(FWHM), which shows mainly the infarct core. CONCLUSION: We have shown here, ex vivo, that SI-PIM has the same advantages as R1-PIM, but it is based on the scanning sequences of DE imaging, and thus it is obtainable within the same short scanning time as DE. This makes it a practical method for clinical studies.

Differentiation of acute and four-week old myocardial infarct with Gd(ABE-DTTA)-enhanced CMR.

BACKGROUND: Standard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older myocardial infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older myocardial infarct using myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent.Dogs (n = 6) were studied in a closed-chest, reperfused, double myocardial infarct model. Myocardial infarcts were generated by occluding the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumflex (LCx) coronary artery for 180 min. LE images were obtained on day 3 and day 4 after second myocardial infarct, using Gd(DTPA) (standard extracellular contrast agent) and Gd(ABE-DTTA) (new, low molecular weight contrast agent), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of infarcts. Hematoxylin-eosin and Masson's trichrome staining provided histologic evaluation of infarcts. RESULTS: Gd(ABE-DTTA) or Gd(DTPA) highlighted the acute infarct, whereas the four-week old infarct was visualized by Gd(DTPA), but not by Gd(ABE-DTTA). With Gd(ABE-DTTA), the mean +/- SD signal intensity enhancement (SIE) was 366 +/- 166% and 24 +/- 59% in the acute infarct and the four-week old infarct, respectively (P < 0.05). The latter did not differ significantly from signal intensity in healthy myocardium (P = NS). Gd(DTPA) produced signal intensity enhancements which were similar in acute (431 +/- 124%) and four-week old infarcts (400 +/- 124%, P = NS), and not statistically different from the Gd(ABE-DTTA)-induced SIE in acute infarct. The existence and localization of both infarcts were confirmed by triphenyltetrazolium chloride (TTC). Histologic evaluation demonstrated coagulation necrosis, inflammation, and multiple foci of calcification in the four day old infarct, while the late subacute infarct showed granulation tissue and early collagen deposition. CONCLUSIONS: Late enhancement CMR with separate administrations of standard extracellular contrast agent, Gd(DTPA), and the new low molecular weight contrast agent, Gd(ABE-DTTA), differentiates between acute and late subacute infarct in a reperfused, double infarct, canine model.

Virtual in vivo biopsy map of early prostate neoplasm in TRAMP mice by MRI.

BACKGROUND: The noninvasive, early detection of Prostate Intraepithelial Neoplasia (PIN), a precancerous neoplasia of the prostate, would be highly desirable. In our experiments, we used TRAMP mice to model PIN in the range of grade 1 through grade 4. METHODS: Contrast enhanced pixel-by-pixel R1 mapping of the prostate was used to detect areas with the different prostate neoplasia grades. After anesthesia, Gd(ABE-DTTA) was injected I.V. A series of MRI images with varying TI were then acquired to create R1 maps in a 2 mm transversal tomographic slice that included the prostate. After euthanasia and the excision of the prostate, a 2 mm slice, corresponding to the tomographic slice, was selected and prepared for histological analysis. The microscopic sections of this slice were scanned and analyzed along with the R1 maps. The R1 values were normalized to that measured in muscle tissue in each individual mouse to account for possible variations among the mice in contrast agent uptake (R1(norm)). The R1(norm) values and the histological grades in the corresponding areas were correlated. RESULTS: A significant difference was found between the R1(norm) values measured in areas with grade 1-2 versus those observed in areas with grades 3-4. Also, a significant correlation was found between the area size of the ROIs differentiated by MRI, and those determined by histology. CONCLUSION: This method has the potential for early noninvasive detection of developing prostate cancer.

Myocardial tissue characterization by combining late gadolinium enhancement imaging and percent edema mapping: a novel T2 map-based MRI method in canine myocardial infarction.

BACKGROUND: Assessing the extent of ischemic and reperfusion-associated myocardial injuries remains challenging with current magnetic resonance imaging (MRI) techniques. Our aim was to develop a tissue characterization mapping (TCM) technique by combining late gadolinium enhancement (LGE) with our novel percent edema mapping (PEM) approach to enable the classification of tissue represented by MRI voxels as healthy, myocardial edema (ME), necrosis, myocardial hemorrhage (MH), or scar. METHODS: Six dogs underwent closed-chest myocardial infarct (MI) generation. Serial MRI scans were performed post-MI on days 3, 4, 6, 14, and 56, including T2 mapping and LGE. Dogs were sacrificed on day 4 (n = 4, acute MI) or day 56 (n = 2, chronic MI). TCMs were generated based on a voxel classification algorithm taking into account signal intensity from LGE and T2-based estimation of ME. TCM-based MI and MH were validated with post mortem triphenyl tetrazolium chloride (TTC) staining. Pearson's correlation and Bland-Altman analyses were performed. RESULTS: The MI, ME, and MH measured by TCM were 13.4% [25th-75th percentile 1.6-28.8], 28.1% [2.1-37.5] and 4.3% [1.0-11.3], respectively. TCM measured higher MH and MI compared to TTC (p = 0.0033 and p = 0.0007, respectively). MH size was linearly correlated with MI size by both MRI (r = 0.9528, p < 0.0001) and TTC (r = 0.9625, p < 0.0001). MH quantification demonstrated good agreement between TCM and TTC (r = 0.8766, p < 0.0001, 2.4% overestimation by TCM). A similar correlation was observed for MI size (r = 0.9429, p < 0.0001, 6.1% overestimation by TCM). CONCLUSIONS: Preliminary results suggest that the TCM method is feasible for the in vivo localization and quantification of various MI-related tissue components.

Equilibrium signal intensity mapping, an MRI method for fast mapping of longitudinal relaxation rates and for image enhancement.

INTRODUCTION: Inhomogeneity of magnetic fields, both B(0) and B(1), has been a major challenge in magnetic resonance imaging (MRI). Field inhomogeneity leads to image artifacts and unreliability of signal intensity (SI) measurements. This work proposes and shows the feasibility of generating equilibrium signal intensity (SI(Eq)) maps that can be utilized either to speed up relaxation-rate measurement or to enhance image quality and relaxation-rate-based weighting in various applications. METHODS: A 1.5-T MRI scanner was used. In canines (n=4), myocardial infarction was induced, and 48 h after the administration of 0.05 mmol kg(-1) Gd(ABE-DTTA), a contrast agent with slow tissue kinetics, in vivo R(1) mapping was carried out using an inversion recovery (IR)-prepared, fast gradient-echo sequence with varying inversion times (TIs). To test the SI(Eq) mapping method without the confounding effects of motion and blood flow, we carried out ex vivo R(1) mapping after the administration of 0.2 mmol kg(-1) Gd(DTPA) using an IR-prepared, fast spin-echo sequence in another group of dogs (n=2). R(1,full) maps and SI(Eq) maps were generated from the data from both sequences by three-parameter nonlinear curve fitting of the SI versus TI dependence. R(1,full) maps served as the reference standard. Raw IR images were then divided by the SI(Eq) maps, yielding corrected SI maps (COSIMs). Additionally, R(1) values were calculated from each single-TI image separately, using the SI(Eq) value and a one-parameter curve-fitting procedure (R(1,single)). Voxelwise correlation analysis was carried out for the COSIMs and the R(1,single) maps, both versus the standard R(1,full) maps. Deviations of R(1,single) from R(1,full) were statistically evaluated. RESULTS: In vivo, COSIM versus R(1,full) showed significantly (P<.05) better correlation [correlation coefficient (CC)=0.95] than SI versus R(1,full) with a TI=700-800 ms, which is 200-300 ms longer than the tau(null) (500 ms) of viable myocardium. With such TIs, SI versus R(1,full) yielded CCs of 0.86-0.88. R(1,single) versus R(1,full) yielded a peak CC of 0.96 at TI=700-900 ms. Mean deviations of R(1,single) from R(1,full) were below 5% for TIs between 500 and 1000 ms. Ex vivo, where tau(null) was 300 ms, the advantage of correction with SI(Eq) was not in the improvement of linear correlation but more in the reduction of scatter. Peak CCs for SI versus R(1,full) and COSIM versus R(1,full) at TI=500 ms were 0.96 for both. The ex vivo CC for R(1,single) versus R(1,full) at TI=500 ms was 0.98. Mean deviations of R(1,single) from R(1,full) were below 5% for TIs between 400 and 700 ms. CONCLUSIONS: Once the corresponding SI(Eq) map is obtained from a control stack, R(1) can be obtained accurately, using only a single IR image and without the need for a stack of TI-varied images. This approach could be applied in various dynamic MRI studies where short measurement time, once the dynamics has started, is of essence. When using this method with IR-prepared T(1)-weighted images, it is essential that the single TI be chosen such that the longitudinal relaxation in all voxels of interest would have passed tau(null). SI(Eq) maps are also useful in eliminating confounders from MR images to allow obtaining SI values that reflect more faithfully the relaxation parameter (R(1)) sought.

The MRI characteristics of the no-flow region are similar in reperfused and non-reperfused myocardial infarcts: an MRI and histopathology study in swine.

BACKGROUND: The no-flow region (NF) visualised by magnetic resonance imaging (MRI) in myocardial infarction (MI) has been explained as the product of reperfusion-injury-induced microvascular obstruction. However, a similar MRI phenomenon occurs in non-reperfused MI. Accordingly, our purpose was to compare the MRI and histopathologic characteristics of the NF in reperfused and non-reperfused MIs. METHODS: Reperfused (n = 7) and non-reperfused MIs (n = 7) were generated in swine by percutaneous balloon occlusion and microsphere embolisation techniques. Four days post-MI, animals underwent myocardial T2-mapping, early and serial late gadolinium enhancement MRI. MI and NF were compared between the models using the independent samples t test. Serial measurements were analysed using repeated measures analysis of variance. Triphenyltetrazolium chloride (TTC) macroscopic and microscopic histopathologic assessment was also performed. RESULTS: The MI size in the reperfused and non-reperfused groups was 17.1 ± 3.4 ml and 19.4 ± 8.1 ml, respectively (p = 0.090), in agreement with TTC assessment (p = 0.216; p = 0.484), and the NF size was 7.7 ± 2.4 ml and 8.1 ± 1.9 ml, respectively (P = 0.211). Compared to the reference 2-min post-contrast measurement, the NF size was significantly reduced at 20 min in the reperfused group and at 25 min in the non-reperfused group (both p < 0.001). Nevertheless, the NF was still detectable at 45 min after injection. No significant T2 difference was observed between the groups (p > 0.326). Histopathologic assessment revealed extensive calcification and hemosiderin deposition in the NF of the reperfused MI, but not in the non-reperfused MI. CONCLUSIONS: The NF in non-reperfused and reperfused MIs have similar characteristics on MRI despite the different pathophysiologic and underlying histopathologic conditions, indicating that the presence of the NF alone cannot differentiate between these two types of MI.

In Vitro Longitudinal Relaxivity Profile of Gd(ABE-DTTA), an Investigational Magnetic Resonance Imaging Contrast Agent.

PURPOSE: MRI contrast agents (CA) whose contrast enhancement remains relatively high even at the higher end of the magnetic field strength range would be desirable. The purpose of this work was to demonstrate such a desired magnetic field dependency of the longitudinal relaxivity for an experimental MRI CA, Gd(ABE-DTTA). MATERIALS AND METHODS: The relaxivity of 0.5mM and 1mM Gd(ABE-DTTA) was measured by Nuclear Magnetic Relaxation Dispersion (NMRD) in the range of 0.0002 to 1T. Two MRI and five NMR instruments were used to cover the range between 1.5 to 20T. Parallel measurement of a Gd-DTPA sample was performed throughout as reference. All measurements were carried out at 37°C and pH 7.4. RESULTS: The relaxivity values of 0.5mM and 1mM Gd(ABE-DTTA) measured at 1.5, 3, and 7T, within the presently clinically relevant magnetic field range, were 15.3, 11.8, 12.4 s-1mM-1 and 18.1, 16.7, and 13.5 s-1mM-1, respectively. The control 4 mM Gd-DTPA relaxivities at the same magnetic fields were 3.6, 3.3, and 3.0 s-1mM-1, respectively. CONCLUSIONS: The longitudinal relaxivity of Gd(ABE-DTTA) measured within the presently clinically relevant field range is three to five times higher than that of most commercially available agents. Thus, Gd(ABE-DTTA) could be a practical choice at any field strength currently used in clinical imaging including those at the higher end.

Determination of infarct size in ex vivo swine hearts by multidetector computed tomography using gadolinium as contrast medium.

OBJECTIVE: To demonstrate the feasibility of using multidetector computed tomography with gadolinium contrast (Gd-MDCT) for the quantification of myocardial infarct (MI). MATERIALS AND METHODS: MI was induced in male swine (n = 6). One week later, the animals received 0.2-mmol/kg gadopentetate dimeglumine and were sacrificed. On the excised hearts, Gd-MDCT with several tube voltages (80, 120, and 140 kV), late gadolinium enhancement MRI (LGE-MRI), and triphenyl-tetrazolium-chloride staining were then conducted. We used a 2-SD threshold for the CT images and several threshold limits (2, 3, 4, 5, 6 SD, and full width at half-maximum [FWHM]) for the LGE-MRI images to delineate the infarct area. Total infarct volume and infarct fraction of each heart were calculated. RESULTS: MI size measured by MDCT at 140 kV showed good correlation with the reference triphenyl-tetrazolium-chloride value. Applying an 80-kV tube voltage, however, significantly underestimated MI size. In our study, the LGE-MRI method, using the 6-SD threshold, provided the most accurate determination of MI size. LGE-MRI, using the 2- and 3-SD threshold limits, significantly overestimated infarct size. CONCLUSIONS: The Gd-MDCT technique has been found suitable for the evaluation of MI in an ex vivo experimental setting. Gd-MDCT has the ability to detect MI even at low kV settings, but accuracy is limited by a high image noise because of reduced photon flux.

Acute infarct selective MRI contrast agent.

To determine the infarct affinity of a low molecular weight contrast agent, Gd(ABE-DTTA), during the subacute phase of myocardial infarct (MI). Dogs (n = 7) were examined, using a closed-chest, reperfused MI model. MI was generated by occluding for 180 min the left anterior descending (LAD) coronary artery with an angioplasty balloon. DE-MRI images with Gd(ABE-DTTA) were obtained on days 4, 14, and 28 after MI. Control DE-MRI by Gd(DTPA) was carried out on day 27. T2-TSE images were acquired on day 3, 13 and 27. Triphenyltetrazolium chloride (TTC) histomorphometry validated postmortem the existence of infarct. Gd(ABE-DTTA) highlighted the infarct on day 4, but not at all on day 14 or on day 28, following MI. On day 4, the mean ± SD signal intensity (SI) of infarcted myocardium in the presence of Gd(ABE-DTTA) significantly differed from that of healthy myocardium (45 ± 6.0 vs. 10 ± 5.0, P < 0.05), but it did not on day 14 (11 ± 9.4 vs. 10 ± 5.7, P = NS), nor on day 28 (7 ± 1.5 vs. 7 ± 2.4, P = NS). The mean ± SD signal intensity enhancement (SIE) induced by Gd(ABE-DTTA) was 386 ± 165% on day 4, significantly different from mean SIE on day 14 (9 ± 20%), and from mean SIE on day 28 (12 ± 18%), following MI (P < 0.05). The last two mean values did not differ significantly (P = NS) from each other. As control, Gd(DTPA) was used and it did highlight the infarct on day 27, inducing a mean SIE value of 312 ± 40%. The mean SIE on day 3, 13, or 27 did not vary significantly (P = NS) on the T2-TSE images (114 ± 41%, 123 ± 41%, and 150 ± 79%, respectively). Post mortem, the existence of infarcts was confirmed by TTC staining. The infarct affinity of Gd(ABE-DTTA) vanishes in the subacute phase of scar healing, allowing its use for infarct age differentiation early on, immediately following the acute phase.

Myocardial strain in sub-acute peri-infarct myocardium.

PURPOSE: In the absence of additional ischemic insults, the peri-infarct region surrounding the infarct myocardium can recover function. T2 weighted MRI signal is sensitive to edema and used to detect peri-infarct, salvageable myocardium. The main purpose of this study was to investigate the alterations in myocardial strain in the peri-infarct myocardium as compared to normal and infarct myocardium. MATERIALS AND METHODS: Comprehensive MRI of the myocardium was performed in five pigs 6-7 days following coronary artery occlusion-reperfusion myocardial injury. MRI included tagged cine images for myocardial strain, T2weighted (T2w)-images and late gadolinium enhancement (LGE) for assessing myocardial viability. Automated signal intensity thresholds were used to define tissue edema and myocardial infarct. Maximum-shortening strains were analyzed in the infarct, peri-infarct and normal myocardial sectors. The results were correlated with triphenyltetrazolium-chloride (TTC) and hemotoxylin-eosin stained tissue images. RESULTS: We found an excellent correlation of LGE with TTC (r = 0.94, P < 0.05). T2w-images markedly overestimated the infarct size (25 +/- 3%). Both the healthy and peri-infarct myocardial sectors had higher myocardial strain than infarct myocardial sectors (P < 0.05). Clear demarcation between infarct and non-infarct myocardium was noted on histology. CONCLUSION: Peri-infarct myocardium continues to demonstrate T2 signal enhancement to at least 7 days, but this region has preserved mechanical function. T2-weighted imaging and myocardial strain measurements provide complementary information and both may be useful for characterization of the peri-infarct myocardium.

Head-to-head comparison between delayed enhancement and percent infarct mapping for assessment of myocardial infarct size in a canine model.

PURPOSE: To compare a novel method, percent-infarct-mapping (PIM), with conventional delayed enhancement (DE) of contrast for accurate myocardial viability assessment. Contrary to signal intensity (SI), the longitudinal relaxation-rate enhancement (DeltaR1) is an intrinsic parameter linearly proportional to the concentration of contrast agent (CA). Determining DeltaR1 voxel-by-voxel, after administering an infarct-avid CA, allows determination of per-voxel percentage of infarcted tissue. The feasibility of generating PIM is demonstrated in canine reperfused infarction using an infarct-avid, persistent-CA (PCA), (Gd)(ABE-DTTA). PIM is compared to the DE method using Gd(DTPA), and both to triphenyltetrazolium chloride (TTC) staining histochemistry. MATERIALS AND METHODS: In six dogs, 48 hours following closed-chest, 180-minute coronary occlusion, DE imaging was carried out. PCA was administered immediately thereafter. Pixel-by-pixel R1 maps of the entire left ventricle (LV) were generated 48 hours after PCA using inversion-recovery with multiple inversion times. R1, DeltaR1, and percent-infarct values were calculated voxel-by-voxel. RESULTS: Significant correlations (P < 0.01, R >or= 0.8) were obtained for percent-infarct-per-slice (PIS) determined by DE or PIM vs. those from corresponding TTC-stained slices. Compared to TTC, DE overestimated PIS by 32 +/- 18%. PIM underestimated PIS by 2.5 +/- 4.9%. Infarction fraction overestimation was 29 +/- 6% of LV by DE, but only 1.0 +/- 2.3% by PIM. Errors with PIM were significantly smaller than those with DE. Infarct area determined by signal intensity was similarly overestimated whether using Gd(DTPA) or Gd(ABE-DTTA). CONCLUSION: The DeltaR1-based PIM method is highly reproducible and more accurate than DE for quantifying myocardial viability in vivo.

Automated multidetector computed tomography evaluation of subacutely infarcted myocardium.

BACKGROUND: Delayed enhanced (DE) multidetector computed tomography (MDCT) can identify acute and chronic myocardial infarct. To our knowledge, automated techniques for infarct quantification on DE-MDCT have not been used. OBJECTIVE: We evaluated an automated signal intensity (SI) threshold method for quantification of subacute myocardial infarct and identified and quantified microvascular obstruction (MO) in subacute infarct. METHODS: DE-MDCT imaging was performed on 5 pigs 6-7 days after mid left anterior descending artery occlusion-reperfusion. DE-MDCT images were compared with triphenyl tetrazolium chloride (TTC) staining for infarct quantification and with hematoxylin and eosin (H&E) staining for MO quantification. Pixels with SI more than the mean SI of a remote normal myocardial region (SI(remote)) plus 2 times the standard deviation (SI(remote) + 2 SD) value were considered infarct pixels. The ratio of infarct to total area of a given slice, the percentage of infarct area per slice (PIS), was calculated. MO as a percentage of total infarct area was also calculated. RESULTS: The average density values on DE-MDCT (5 minutes after contrast injection) were remote normal myocardium of 93 +/- 19 Hounsfield units (HU), infarct myocardium of 159 +/- 40 HU, blood of 140 +/- 26 HU, and MO of 85 +/- 30 HU. PIS(MDCT) showed substantial agreement with PIS(TTC) (y = 1.003x + 4.12; R = 0.90, P < 0.05). A relation was also shown between MO determined by MDCT compared with H&E staining (y = 0.74x + 3.4). CONCLUSIONS: We show the feasibility of using a semiautomated SI threshold technique for quantification of subacute myocardial infarct. We also show the persistent MO in subacute myocardial infarct on DE-MDCT images.

A combined method for the determination of myocardial perfusion in experimental animals using microspheres and CMR.

A convenient method is introduced for myocardial perfusion research by combining multislice short-axis cine cardiovascular magnetic resonance (MSA-CMR) and colored microspheres (CM). In canine control-ischemia-reperfusion (n = 11), Cardiac output (CO) was measured using MSA-CMR (COMSA), Phase Contrast CMR (PC-CMR, COPC) and CM (from reference blood samples, COmicro) in 3 experimental periods per animal. COmicro significantly and systematically overestimated COMSA (median deviation: 291 mL/min, p < 0.01), while there was excellent agreement between PC-CMR and MSA-CMR without significant over-or underestimation (median deviation: -14 ml/min, p = NS). In quantitative myocardial perfusion assay by CM, CMR should be used instead of reference blood sampling. This should improve the accuracy of absolute regional perfusion measurement.

In vivo myocardial tissue kinetics of Gd(ABE-DTTA), a tissue-persistent contrast agent.

The phenomenological tissue kinetics of Gd(ABE-DTTA) was investigated in myocardial infarction (MI). Reperfused infarction was generated by balloon catheter in closed-chest canines (N=11). Forty-eight hours thereafter, inversion-recovery (IR)-prepared fast gradient-echo control images were acquired with varying inversion times (TIs). Precontrast R(1) maps were calculated from the TI dependence of signal intensity (SI) using nonlinear curve fitting. Then 0.05 mmol/kg Gd(ABE-DTTA) was administered I.V. In 11 dogs postcontrast R(1) maps were generated at 24 hr and 48 hr postcontrast. In five dogs measurements were also repeated at 108 hr and 12 days. In one dog early measurement was carried out at 4 hr. Delta R(1) values for blood and viable and infarcted myocardium were calculated at each time point by subtracting the precontrast R(1) from the postcontrast R(1). Gd(ABE-DTTA) showed significant, progressive accumulation into infarcts during the first 2 days (k(in)=0.39 hr(-1)) and a delayed clearance (k(out) = 0.005 hr(-1)). Among the time points sampled, the maximum infarct Delta R(1) was detected at 48 hr (1.72 s(-1)). Contrast agent (CA) in infarcted tissue was detectable for 12 days. Clearance from blood and viable myocardium occurred in parallel and was completed by 108 hr. Gd(ABE-DTTA) displays slow, tissue-persistent kinetics and partly intravascular, partly extravascular characteristics. It demonstrates high affinity for infarcted myocardium and induces highlighting of infarcts between 4 hr and 12 days following administration.

Percent infarct mapping: an R1-map-based CE-MRI method for determining myocardial viability distribution.

Viability detection is crucial for the management of myocardial infarction (MI). Signal intensity (SI)-based MRI methods may overestimate infarct size in vivo. In contrast to SI, the longitudinal relaxation-rate enhancement (DeltaR1) is an intrinsic parameter that is linearly proportional to the concentration of contrast agent (CA). Determining DeltaR1 in the presence of an infarct-avid persistent CA (PCA) allows determination of the per-voxel percentage of infarcted tissue. Introduced here is a DeltaR1-based CE-MRI method, termed percent infarct mapping (PIM), for quantifying myocardial viability following delayed PCA accumulation. In a canine MI model (N=6), PIMs were generated using a persistent CA (PCA) and validated using triphenyltetrazolium-chloride (TTC) histochemistry. Voxel-by-voxel R1 maps of the entire left ventricle (LV) were generated 24 and 48 hr after PCA administration using inversion recovery (IR) with multiple inversion times (TIs). PI values were calculated voxel by voxel. Significant correlations (P<0.01, R=0.97) were obtained for PI per slice (PIS) determined using PIM vs. corresponding TTC-based values. Median deviations of PIS with PIM from that with TTC were only 1.01% and -0.53%, at 24 hr and 48 hr. Median deviations from the true infarction fraction (IF) were 1.23% and 0.49% of LV at 24 hr and 48 hr, respectively. No significant difference was found between PIM24 hr and PIM48 hr. DeltaR1-based PIM is an accurate and reproducible method for quantifying myocardial viability distribution, and thus enhances the clinical utility of CE-MRI.

Gd(ABE-DTTA), a novel contrast agent, at the MRI-effective dose shows absence of deleterious physiological effects in dogs.

The physiological effects of a novel MRI contrast agent, Gd(ABE-DTTA), were investigated in dogs, monitoring parameters in blood samples. Each animal (n = 8 in the short-term, n = 4 in the long-term group) underwent isoflurane anesthesia followed by the generation of myocardial infarction and received a contrast agent at the MRI effective dose. Blood samples were collected 24 and 48 h, and 7, 14, 28, 35, 49 and 56 days after contrast agent administration. No significant changes exceeding the normal range were detected in any of the investigated parameters except in alanine aminotransferase (ALT). ALT enzyme activity increased in the short-term group 24 and 48 h after agent administration as expected from the effect of isoflurane anesthesia. Between days 7 and 56 no elevation in ALT was observed. In dogs no substantial short- or long-term effect was observed on the investigated, physiological parameters after Gd(ABE-DTTA) administration at the MRI effective dose.