Pál Kiss

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 (ΔR1) is an intrinsic parameter that is linearly proportional to the concentration of contrast agent (CA). Determining ΔR1 in the presence of an infarct‐avid persistent CA (PCA) allows determination of the per‐voxel percentage of infarcted tissue. Introduced here is a ΔR1‐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. ΔR1‐based PIM is an accurate and reproducible method for quantifying myocardial viability distribution, and thus enhances the clinical utility of CE‐MRI. Magn Reson Med, 2006.

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

BackgroundStandard 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 Massons trichrome staining provided histologic evaluation of infarcts.ResultsGd(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.ConclusionsLate 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.

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

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.

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.

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.

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

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 (ΔR1) is an intrinsic parameter linearly proportional to the concentration of contrast agent (CA). Determining ΔR1 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.

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

To develop a magnetic resonance imaging (MRI) compatible, percutaneous technique for the generation of nonreperfused myocardial infarct (MI).

In vivo R1-enhancement mapping of canine myocardium using ceMRI with Gd(ABE-DTTA) in an acute ischemia-reperfusion model

To demonstrate the usefulness of normalized ΔR1 (ΔR1n) mapping in myocardial tissue following the administration of the contrast agent (CA) Gd(ABE‐DTTA).

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 R1 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 R1 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. ΔR1 values for blood and viable and infarcted myocardium were calculated at each time point by subtracting the precontrast R1 from the postcontrast R1. Gd(ABE‐DTTA) showed significant, progressive accumulation into infarcts during the first 2 days (kin = 0.39 hr–1) and a delayed clearance (kout = 0.005 hr–1). Among the time points sampled, the maximum infarct ΔR1 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. Magn Reson Med 58:55–64, 2007.

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.