Cronkhite­Canada syndrome / Cronkhite-Canada-szindróma.

Összefoglaló. A Cronkhite-Canada-szindróma egy extrém ritka, nem öröklodo, gyomor-bél rendszeri polyposissal, fehérjeveszto enteropathiával és ectodermalis elváltozásokkal járó megbetegedés. A világon eddig összesen körülbelül 500 esetet jegyeztek fel. Az etiológia pontosan nem tisztázott, hátterében elsosorban autoimmun folyamatot feltételeznek. A diagnózis a páciens kórtörténetén, a fizikális vizsgálaton, az endoszkópos képen és a szövettani leleten alapul. A jelen közleményben egy 71 éves férfi beteg esetét mutatjuk be. A klinikai kép és az elvégzett vizsgálatok alapján a tünetek hátterében Cronkhite-Canada-szindrómát igazoltunk, majd a szakirodalomban leggyakrabban alkalmazott kombinált protonpumpagátló, kortikoszteroid és meszalazin adását vezettük be, illetve táplálásterápiát alkalmaztunk. Tudomásunk szerint Cronkhite-Canada-szindrómás beteg esete Magyarországon elsoként kerül ismertetésre. Orv Hetil. 2021; 162(11): 432-438. Summary. Cronkhite-Canada syndrome is an extremely rare, noninherited disease, characterized by gastrointestinal polyposis, protein-losing enteropathy and ectodermal abnormalities. Approximately 500 cases have been reported worldwide. The aetiology is unknown, most probably autoimmune mechanisms may be involved. The diagnosis is based on patient history, physical examination, endoscopic findings and histology. Here we report the case of a 71-year-old male, diagnosed with Cronkhite-Canada syndrome. The treatment consisted of proton-pump inhibitor, corticosteroids, mesalazin and nutritional therapy. To the best of our knowledge, this is the first report of Cronkhite-Canada syndrome in Hungary. Orv Hetil. 2021; 162(11): 432-438.

Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis.

BACKGROUND: Previously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients' responsiveness to anti-VEGF therapy. RESULTS: One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r = 0.29, P = 0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r = 0.34, p = 0.0007) but not in healthy controls (r = 0.057, p = 0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients' responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls. CONCLUSIONS: Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.

Processing Analysis of Nanoparticle Filled PTFE: Restrictions and Limitations of High Temperature Production.

In this research work, unfilled and monofilled polytetrafluoroethylene (PTFE) were investigated. The applied fillers were graphene, alumina (Al2O3), boehmite alumina (BA80) and hydrotalcite (MG70). Graphene and Al2O3 are already known in the literature as potential fillers of PTFE, while BA80 and MG70 are novel fillers in PTFE. Materials were produced by room temperature pressing-free sintering method with a maximum sintering temperature of 370 °C. The mass loss and decomposition analyses were carried out by thermogravimetric analysis (TGA) in two different ways. The first was a sensitivity analysis to gain a better view into the sintering process at 370 °C maximal temperature. The second was a heating from 50 °C up to 1000 °C for a full-scale decomposition analysis. BA80 is a suitable filler for PTFE, as most of its functional groups still existed after the sintering process. Both PTFE and Al2O3 had high thermal stability. However, when Al2O3 was incorporated in PTFE, a remarkable mass loss was observed during the sintering process, which indicated that the decomposition of PTFE was catalysed by the Al2O3 filler. The observed mass loss of the Al2O3-filled PTFE was increased, as the Al2O3 content or the applied dwelling time at a 370 °C sintering temperature increased.

Thermal, Viscoelastic, Mechanical and Wear Behaviour of Nanoparticle Filled Polytetrafluoroethylene: A Comparison.

In this research work, unfilled and mono-filled polytetrafluoroethylene (PTFE) materials were developed and characterised by physical, thermal, viscoelastic, mechanical, and wear analysis. The applied fillers were graphene, alumina (Al2O3), boehmite alumina (BA80), and hydrotalcite (MG70) in 0.25/1/4/8 and 16 wt % filler content. All samples were produced by room temperature pressing-free sintering method. All of the fillers were blended with PTFE by intensive dry mechanical stirring; the efficiency of the blending was analysed by Energy-dispersive X-ray spectroscopy (EDS) method. Compared to neat PTFE, graphene in 4/8/16 wt % improved the thermal conductivity by ~29%/~84%/~157%, respectively. All fillers increased the storage, shear and tensile modulus and decreased the ductility. PTFE with 4 wt % Al2O3 content reached the lowest wear rate; the reduction was more than two orders of magnitude compared to the neat PTFE.

Surgical treatment of heart failure due to giant coronary artery fistula: a case report.

Coronary artery fistula is a rare congenital cardiac anomaly that is often found incidentally during computed tomography angiography. Coronary fistula between the left circumflex coronary artery and the coronary sinus is among the less common forms of coronary artery fistula. A 60-yea\r-old female patient presented to our outpatient cardiology department with symptoms of severe, de novo heart failure. Echocardiogram revealed severe mitral regurgitation and a dilated duct that turbulently accelerated colour Doppler flow behind the left ventricle with significant left-to-right shunt. Cardiac magnetic resonance imaging and computed tomography angiography revealed a massively dilated fistula between the left circumflex coronary artery and the coronary sinus with a diameter of 3-4 cm. The patient underwent combined heart surgery involving mitral ring annuloplasty and fistula ligation and was discharged in stable condition on guideline-based medical therapy. At 18 months of follow-up, minimal residual shunt flow and mild-to-moderate mitral regurgitation were found. We report a rare case of congenital coronary disorder resulting in heart failure and highlight the importance of complex non-invasive cardiac diagnostic procedures before planning and performing heart surgery.

The Effect of Multilevel Carbon Reinforcements on the Fire Performance, Conductivity, and Mechanical Properties of Epoxy Composites.

We studied the effect of a multilevel presence of carbon-based reinforcements-a combination of conventional load-bearing unidirectional carbon fiber (CF) with multiwalled carbon nanotubes (CNT) and conductive CNT-containing nonwoven carbon nanofabric (CNF(CNT))-on the fire performance, thermal conductivity, and mechanical properties of reference and flame-retarded epoxy resin (EP) composites. The inclusion of carbon fibers and flame retardant reduced the peak heat release rate (pHRR) of the epoxy resins. The extent to which the nanoreinforcements reduced the pHRR depended on their influence on thermal conductivity. Specifically, high thermal conductivity is advantageous at the early stages of degradation, but after ignition it may lead to more intensive degradation and a higher pHRR; especially in the reference samples without flame retardant. The lowest pHRR (130 kW/m²) and self-extinguishing V-0 UL-94 rating was achieved in the flame-retarded composite containing all three levels of carbon reinforcement (EP + CNF(CNT) + CNT + CF FR). The plasticizing effect of the liquid flame retardant impaired both the tensile and flexural properties; however, it significantly enhanced the impact resistance of the epoxy resin and its composites.

Transcriptional Alterations by Ischaemic Postconditioning in a Pig Infarction Model: Impact on Microvascular Protection.

Although the application of cardioprotective ischaemia/reperfusion (I/R) stimuli after myocardial infarction (MI) is a promising concept for salvaging the myocardium, translation to a clinical scenario has not fulfilled expectations. We have previously shown that in pigs, ischaemic postconditioning (IPostC) reduces myocardial oedema and microvascular obstruction (MVO), without influencing myocardial infarct size. In the present study, we analyzed the mechanisms underlying the IPostC-induced microvascular protection by transcriptomic analysis, followed by pathway analysis. Closed-chest reperfused MI was induced by 90 min percutaneous balloon occlusion of the left anterior descending coronary artery, followed by balloon deflation in anaesthetised pigs. Animals were randomised to IPostC (n = 8), MI (non-conditioned, n = 8), or Control (sham-operated, n = 4) groups. After three hours or three days follow-up, myocardial tissue samples were harvested and subjected to RNA-seq analysis. Although the transcriptome analysis revealed similar expression between IPostC and MI in transcripts involved in cardioprotective pathways, we identified gene expression changes responding to IPostC at the three days follow-up. Focal adhesion signaling, downregulated genes participating in cardiomyopathy and activation of blood cells may have critical consequences for microvascular protection. Specific analyses of the gene subsets enriched in the endothelium of the infarcted area, revealed strong deregulation of transcriptional functional clusters, DNA processing, replication and repair, cell proliferation, and focal adhesion, suggesting sustentative function in the endothelial cell layer protection and integrity. The spatial and time-dependent transcriptome analysis of porcine myocardium supports a protective effect of IPostC on coronary microvasculature post-MI.

Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension.

BACKGROUND: Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. METHODS: For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload. Five pigs with sham intervention served as control. Serial haemodynamic, pressure-volume loop measurements and transthoracic echocardiography (TTE) were performed to detect developing pressure overload of the LV and cardiac MRI with late enhancement for measuring LV and RV mass and ejection fraction. RESULTS: At 5-month follow-up, CT and contrast aortography, and intraluminal echocardiography confirmed aortic isthmus stenosis with a mean trans-stenotic gradient of 64 ± 13.9 mmHg. Invasive haemodynamic measurements revealed a secondary increase in pulmonary artery pressure (44.6 ± 5.1 vs 25.9 ± 6.2 mmHg, HYPI vs control, p < 0.05). TTE and ex vivo analyses confirmed severe concentric LV hypertrophy (mean circumferential wall thickness, 19.4 ± 3.1, n = 7 vs 11.4 ± 1.0 mm, n = 5, HYPI vs controls, p < 0.05). The LV and RV mass increased significantly, paralleled by increased isovolumic relaxation constant (tau). Histological analyses confirmed substantial fibrosis and myocyte hypertrophy in both LV and RV. Expressions of ANP, BNP, and miRNA-29a were up-regulated, while SERCA2a and miRNA-1 were down-regulated. Plasma NGAL levels increased gradually, while the elevation of NT-proBNP was detected only at the 5-month FUP. CONCLUSION: These data prove that percutaneous artificial aortic stenosis in pigs is useful for inducing clinically relevant progredient heart failure based on myocardial hypertrophy and fibrosis.

In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature.

BACKGROUND: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. METHODS AND RESULTS: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. CONCLUSION: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.

Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8).

BACKGROUND: Infiltrating immune cells including monocytes/macrophages have been implicated in the pathogenesis of neovascular age-related macular degeneration (nAMD). The aim of this study was to investigate the cytokine and chemokine expression and secretion profile of peripheral blood mononuclear cells (PBMCs) from nAMD patients and the relationship between the cytokine/chemokine expression profile and clinical phenotype of nAMD, including macular fibrosis, macular atrophy or the responsiveness to anti-VEGF therapy. METHODS: One hundred sixty-one nAMD patients and 43 controls were enrolled in this study. nAMD patients were divided into subgroups based on the presence/absence of (1) macular atrophy, (2) macular fibrosis and (3) responsiveness to anti-VEGF therapy; 25-30 ml of peripheral blood were obtained from all participants and 5 ml were used for serum collection, and the remaining were used for PBMC isolation using density gradient centrifugation. Intracellular cytokine expressions by PBMCs following phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation were examined using flow cytometry. Cytokine productions in lipopolysaccharides (LPS)-or 1% oxygen -treated PBMC were measured using cytometric bead array (CBA) assay. In addition, cytokine and chemokine levels in the serum were also measured by CBA assay. RESULTS: PBMCs from nAMD patients secreted higher levels of IL-8, CCL2 and VEGF, especially following LPS and 1% oxygen stimulation, than those from controls. 60~80% of IL-8 producing cells were CD11b+CD3- monocytes. The percentage of CD11b+CD3- IL-8+ was significantly increased in nAMD patients compared to controls. PBMCs from nAMD patients without macular fibrosis produced the highest levels of IL-8 and CCL2, whilst PBMCs from nAMD patients with macular atrophy produced highest levels of VEGF. In addition, PBMCs from patients who partially responded to anti-VEGF produced higher levels of IL-8 compared to the cells from complete responders. Interestingly, serum level of CCL2 was not increased in nAMD patients although there was a trend of increased IL-8 in nAMD patients. CONCLUSIONS: PBMCs, in particular monocytes, may contribute to CNV development in nAMD through secreting elevated levels of IL-8, CCL2 and VEGF after they are recruited to the macula. Apart from VEGF, IL-8 and CCL2 may be additional targets for nAMD management.

Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration: Complement activation in AMD.

BACKGROUND: The aim of this study was to investigate the plasma levels of complement C3a, C4a, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients' responsiveness to anti-VEGF therapy. RESULTS: Ninety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case-control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4a and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4a and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4a and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy. CONCLUSIONS: Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.

Age-independent myocardial infarct quantification by signal intensity percent infarct mapping in swine.

PURPOSE: To test whether signal intensity percent infarct mapping (SI-PIM) accurately determines the size of myocardial infarct (MI) regardless of infarct age. MATERIALS AND METHODS: Forty-five swine with reperfused MI underwent 1.5T late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) after bolus injection of 0.2 mmol/kg Gd(DTPA) on days 2-62 following MI. Animals were classified into acute, healing, and healed groups by pathology. Infarct volume (IV) and infarct fraction (IF) were determined by two readers, using binary techniques (including 2-5 standard deviations [SD] above the remote, and full-width at half-maximum) and the SI-PIM method. Triphenyl-tetrazolium-chloride staining (TTC) was performed as reference. Bias (percent under/overestimation of IV relative to TTC) of each quantification method was calculated. Bland-Altman analysis was done to test the accuracy of the quantification methods, while intraclass correlation coefficient (ICC) analysis was done to assess intra- and interobserver agreement. RESULTS: Bias of the MRI quantification methods do not depend on the age of the MI. Full-width at half-maximum (FWHM) and SI-PIM gave the best estimate of MI volume determined by the reference TTC (P-values for the FWHM and SI-PIM methods were 0.183, 0.26, 0.95, and 0.073, 0.091, 0.73 in Group 1, Group 2, and Group 3, respectively), while using any of the binary thresholds of 2-4 SDs above the remote myocardium showed significant overestimation. The 5 SD method, however, provided similar IV compared to TTC and was shown to be independent of the size and age of MI. ICC analysis showed excellent inter- and intraobserver agreement between the readers. CONCLUSION: Our results indicate that the SI-PIM method can accurately determine MI volume regardless of the pathological stage of MI. Once tested, it may prove to be useful for the clinic.

Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-Related Macular Degeneration: 12-Month Safety and Efficacy Outcomes.

PURPOSE: To prospectively assess the safety and efficacy of intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). METHODS: This prospective, non-randomized clinical trial included 49 patients with treatment-resistant nAMD who received 2 mg intravitreal aflibercept as 3 monthly loading doses, followed by injections every 2 months over 12 months. Inclusion criteria included active nAMD on fluorescein angiography at baseline and persistent intra- or subretinal fluid on optical coherence tomography (OCT) for ≥ 6 months prior to baseline with a minimum of 4 injections of bevacizumab and/or ranibizumab. Patients were assessed monthly for best-corrected visual acuity (BCVA), central retinal thickness (CRT) measured with OCT and occurrence of adverse events. Retinal pigment epithelium atrophy (RPEA) was assessed at baseline and at 12 months. RESULTS: Mean BCVA improved by 4.7 letters (95% CI: 2.1-7.3, p < 0.001) and CRT decreased by 97.2 µm (95% CI: 54.4-140.1, p < 0.001) at 12 months compared to baseline. Median RPEA area increased by 0.48 mm2 (range = -0.1 to 19.9, p < 0.001). There was 1 arterial thromboembolic event and 2 cases of submacular haemorrhage. CONCLUSION: In this cohort of treatment-resistant nAMD patients, intravitreal aflibercept was effective in improving vision and reducing exudation. Early visual and anatomic outcomes may predict longer-term response to treatment, but further assessment is required.

Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b(+) cells and CD16(hi)HLA-DR(-) neutrophils were significantly increased (P = 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4(+) T-cells was reduced in nAMD patients without subretinal fibrosis (P = 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b(+) cells and neutrophils are associated with nAMD and that reduced levels of CD4(+) T-cells are associated with the absence of subretinal fibrosis in nAMD.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Outcomes in Eyes With Poor Initial Vision.

PURPOSE: To assess the effect of anti-vascular endothelial growth factor treatment on visual acuity outcome in patients with neovascular age-related macular degeneration presenting with very low vision. METHODS: Retrospective analysis of electronic patient care record of 420 eyes treated with ranibizumab between March 2010 and June 2013. The authors classified the extracted sample into 3 categories based on the initial best-corrected visual acuity (BCVA) as measured on the Early Treatment Diabetic Retinopathy Study charts: 0 to 35 letters, 36 to 69 letters, and ≥ 70 letters. Best BCVA achieved in Year 1, and average BCVA over 36 months was computed. The neovascular lesion type, area of lesion, the presence or absence of hemorrhage, retinal pigment epithelium tear, and atrophy were systematically graded as was extent of fibrosis on a categorical scale of 0 to 4. Regression analysis was performed with the best BCVA achieved in Year 1 as the outcome variable and initial BCVA, person, and lesion characteristics as explanatory variables. RESULTS: The mean change in BCVA from the initial visit to the best-attained BCVA during Year 1 was highly statistically significant with an improvement of 9.95 letters. The improvement from initial BCVA to average BCVA over 36 months was 4.01 letters. Regression analysis identified atrophy and fibrosis as predictors of best BCVA, with the model having an r of 0.71. CONCLUSION: Our study supports the use of anti-vascular endothelial growth factor agents even in eyes with low visual acuity particularly when fibrosis and atrophy are absent and suggests algorithms to predict outcome for combinations of visual acuity and lesion characteristics across the full visual acuity range.

Infarct density distribution by MRI in the porcine model of acute and chronic myocardial infarction as a potential method transferable to the clinic.

To study the feasibility of a myocardial infarct (MI) quantification method [signal intensity-based percent infarct mapping (SI-PIM)] that is able to evaluate not only the size, but also the density distribution of the MI. In 14 male swine, MI was generated by 90 min of closed-chest balloon occlusion followed by reperfusion. Seven (n = 7) or 56 (n = 7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced late gadolinium enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed. MI was quantified using binary [2 or 5 standard deviation (SD)], SI-PIM and R1-PIM methods. Infarct fraction (IF), and infarct-involved voxel fraction (IIVF) were determined by each MRI method. Bias of each method was compared to the TTC technique. The accuracy of MI quantification did not depend on the method of contrast administration or the age of the MI. IFs obtained by either of the two PIM methods were statistically not different from the IFs derived from the TTC measurements at either MI age. IFs obtained from the binary 2SD method overestimated IF obtained from TTC. IIVF among the three different PIM methods did not vary, but with the binary methods the IIVF gradually decreased with increasing the threshold limit. The advantage of SI-PIM over the conventional binary method is the ability to represent not only IF but also the density distribution of the MI. Since the SI-PIM methods are based on a single LGE acquisition, the bolus-data-based SI-PIM method can effortlessly be incorporated into the clinical image post-processing procedure.

Evaluation of experimental myocardial infarction models via electromechanical mapping and magnetic resonance imaging.

The diagnostic characteristics of electromechanical mapping (EMM) were evaluated in porcine myocardial infarction (MI) models with the parallel application of cardiac magnetic resonance imaging (cMRI) from the aspect of different pathophysiology and localization. Balloon occlusion in the left anterior descending coronary artery (LAD balloon group) or coil deployment in the LAD (LAD coil group) or circumflex artery (Cx coil group) was applied percutaneously in 16 domestic pigs. Regional left ventricular viability data were captured via cMRI and EMM. The unipolar voltage (UV) value was significantly decreased in segments containing transmural and subendocardial late enhancement compared with viable segments in the LAD balloon, LAD coil, and Cx coil groups. Receiver operating characteristic analysis revealed area under the curve values of 0.809 and 0.691 in the LAD infarct territory, and 0.864 and 0.855 in the Cx infarct territory for the UV compared with cMRI viability results as transmural late enhancement or viable tissue and subendocardial late enhancement or viable tissue, respectively. In conclusion, the UV value detected the presence of scar tissue with differential transmural extent and which represented proper diagnostic features both in the reperfused and nonreperfused models. This data could provide additional benefit in the clinical use of EMM for diagnostic purposes.

[Dobutamine stress cardiovascular magnetic resonance imaging in patients with peripheral artery disease]. / Dobutaminterheléses szív mágneses rezonanciás vizsgálat alsó végtagi érszukületben szenvedo betegeken.

Patients with peripheral arterial disease often have coronary heart disease, as well. However, their assessment with classical noninvasive cardiology methods is often non-diagnostic or limited. The aim of this study was to analyze the feasibility and the risks of dobutamine stress cardiovascular MRI for cardiac evaluation of patients with peripheral arterial disease. 21 patients with peripheral artery disease (mean±SD age 64.3±7.7 years) were studied prospectively with dobutamine stress cardiovascular MRI. The protocol was completed by all of 21 patients. The target heart rate was attained in 95.2% of the studies. No serious adverse event occurred. The image quality scores (1-4) for all ventricular wall segments were high (median, interquartile range) (4 [4-4]). Five patients (23.8%) have inducible wall motion abnormality. Interobserver agreement was almost perfect for wall motion scores (κ = 0.87, p<0.0001). Dobutamine stress cardiovascular MRI is feasible with low risk for the cardiological assessment of patients with peripheral arterial disease.

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.