Multi-Modality Pathology Segmentation Framework: Application to Cardiac Magnetic Resonance Images

Multi-sequence of cardiac magnetic resonance (CMR) images can provide complementary information for myocardial pathology (scar and edema). However, it is still challenging to fuse these underlying information for pathology segmentation effectively. This work presents an automatic cascade pathology segmentation framework based on multi-modality CMR images. It mainly consists of two neural networks: an anatomical structure segmentation network (ASSN) and a pathological region segmentation network (PRSN). Specifically, the ASSN aims to segment the anatomical structure where the pathology may exist, and it can provide a spatial prior for the pathological region segmentation. In addition, we integrate a denoising auto-encoder (DAE) into the ASSN to generate segmentation results with plausible shapes. The PRSN is designed to segment pathological region based on the result of ASSN, in which a fusion block based on channel attention is proposed to better aggregate multi-modality information from multi-modality CMR images. Experiments from the MyoPS2020 challenge dataset show that our framework can achieve promising performance for myocardial scar and edema segmentation.Comment: 12 pages,MyoPS 202

EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer

<p>Abstract</p> <p>Background</p> <p>As supplement to <it>KRAS </it>mutational analysis<it>, BRAF and PIK3CA </it>mutations as well as expression of PTEN may account for additional non-responders to anti-EGFR-MoAbs treatment. The aim of the present study was to investigate the utility as biomarkers of these mutations in a uniform cohort of patients with metastatic colorectal cancer treated with third-line cetuximab/irinotecan.</p> <p>Methods</p> <p>One-hundred-and-seven patients were prospectively included in the study. Mutational analyses of <it>KRAS, BRAF </it>and <it>PIK3CA </it>were performed on DNA from confirmed malignant tissue using commercially available kits. Loss of PTEN and EGFR was assessed by immunohistochemistry.</p> <p>Results</p> <p>DNA was available in 94 patients. The frequency of KRAS, <it>BRAF </it>and <it>PIK3CA </it>mutations were 44%, 3% and 14%, respectively. All were non-responders. EGF receptor status by IHC and loss of PTEN failed to show any clinical importance. <it>KRAS </it>and <it>BRAF </it>were mutually exclusive. Supplementing <it>KRAS </it>analysis with <it>BRAF </it>and <it>PIK3CA </it>indentified additional 11% of non-responders. Patient with any mutation had a high risk of early progression, whereas triple-negative status implied a response rate (RR) of 41% (p < 0.001), a disease control (DC) rate of 73% (p < 001), and a significantly higher PFS of 7.7(5.1-8.6 95%CI) versus 2.3 months (2.1-3.695%CI) (p < 0.000).</p> <p>Conclusion</p> <p>Triple-negative status implied a clear benefit from treatment, and we suggest that patient selection for third-line combination therapy with cetuximab/irinotecan could be based on triple mutational testing.</p

Cell Therapy for Cardiovascular Disease: A Comparison of Methods of Delivery

The field of myocardial regeneration utilizing novel cell-based therapies, gene transfer, and growth factors may prove to play an important role in the future management of ischemic heart disease and cardiomyopathy. Phases I and II clinical trials have been published for a variety of biologics utilizing four methods of delivery: systemic infusion, intracoronary infusion, transvenous coronary sinus, and intramyocardial. This review discusses the advantages and disadvantages of the delivery approaches above

Analysis of Allogenicity of Mesenchymal Stem Cells in Engraftment and Wound Healing in Mice

Studies have shown that allogeneic (allo-) bone marrow derived mesenchymal stem cells (BM-MSCs) may enhance tissue repair/regeneration. However, recent studies suggest that immune rejection may occur to allo-MSCs leading to reduced engraftment. In this study, we compared allo-BM-MSCs with syngeneic BM-MSCs or allo-fibroblasts in engraftment and effect in wound healing. Equal numbers of GFP-expressing allo-BM-MSCs, syngeneic BM-MSCs or allo-fibroblasts were implanted into excisional wounds in GFP-negative mice. Quantification of GFP-expressing cells in wounds at 7, 14 and 28 days indicated similar amounts of allogeneic or syngeneic BM-MSCs but significantly reduced amounts of allo-fibroblasts. With healing progression, decreasing amounts of allogeneic and syngeneic BM-MSCs were found in the wound; however, the reduction was more evident (2 fold) in allo-fibroblasts. Similar effects in enhancing wound closure were found in allogeneic and syngeneic BM-MSCs but not in allo-fibroblasts. Histological analysis showed that allo-fibroblasts were largely confined to the injection sites while allo-BM-MSCs had migrated into the entire wound. Quantification of inflammatory cells in wounds showed that allo-fibroblast- but not allo-BM-MSC-treated wounds had significantly increased CD45+ leukocytes, CD3+ lymphocytes and CD8+ T cells. Our study suggests that allogeneic BM-MSCs exhibit ignorable immunogenicity and are equally efficient as syngeneic BM-MSCs in engraftment and in enhancing wound healing

Cardiovascular magnetic resonance of myocardial edema using a short inversion time inversion recovery (STIR) black-blood technique: Diagnostic accuracy of visual and semi-quantitative assessment

<p>Abstract</p> <p>Background</p> <p>The short inversion time inversion recovery (STIR) black-blood technique has been used to visualize myocardial edema, and thus to differentiate acute from chronic myocardial lesions. However, some cardiovascular magnetic resonance (CMR) groups have reported variable image quality, and hence the diagnostic value of STIR in routine clinical practice has been put into question. The aim of our study was to analyze image quality and diagnostic performance of STIR using a set of pulse sequence parameters dedicated to edema detection, and to discuss possible factors that influence image quality. We hypothesized that STIR imaging is an accurate and robust way of detecting myocardial edema in non-selected patients with acute myocardial infarction.</p> <p>Methods</p> <p>Forty-six consecutive patients with acute myocardial infarction underwent CMR (day 4.5, +/- 1.6) including STIR for the assessment of myocardial edema and late gadolinium enhancement (LGE) for quantification of myocardial necrosis. Thirty of these patients underwent a follow-up CMR at approximately six months (195 +/- 39 days). Both STIR and LGE images were evaluated separately on a segmental basis for image quality as well as for presence and extent of myocardial hyper-intensity, with both visual and semi-quantitative (threshold-based) analysis. LGE was used as a reference standard for localization and extent of myocardial necrosis (acute) or scar (chronic).</p> <p>Results</p> <p>Image quality of STIR images was rated as diagnostic in 99.5% of cases. At the acute stage, the sensitivity and specificity of STIR to detect infarcted segments on visual assessment was 95% and 78% respectively, and on semi-quantitative assessment was 99% and 83%, respectively. STIR differentiated acutely from chronically infarcted segments with a sensitivity of 95% by both methods and with a specificity of 99% by visual assessment and 97% by semi-quantitative assessment. The extent of hyper-intense areas on acute STIR images was 85% larger than those on LGE images, with a larger myocardial salvage index in reperfused than in non-reperfused infarcts (p = 0.035).</p> <p>Conclusions</p> <p>STIR with appropriate pulse sequence settings is accurate in detecting acute myocardial infarction (MI) and distinguishing acute from chronic MI with both visual and semi-quantitative analysis. Due to its unique technical characteristics, STIR should be regarded as an edema-weighted rather than a purely T2-weighted technique.</p

Cytokine Combination Therapy with Erythropoietin and Granulocyte Colony Stimulating Factor in a Porcine Model of Acute Myocardial Infarction

PurposeErythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.MethodsMI was induced in pigs by a 90&nbsp;min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6&nbsp;weeks post-MI. Histopathology was performed 6&nbsp;weeks post-MI.ResultsAt week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p &lt; 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.ConclusionOur findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF

Troponin release following endurance exercise: is inflammation the cause? a cardiovascular magnetic resonance study

Background: The aetiology and clinical significance of troponin release following endurance exercise is unclear but may be due to transient myocardial inflammation. Cardiovascular magnetic resonance (CMR) affords us the opportunity to evaluate the presence of myocardial inflammation and focal fibrosis and is the ideal imaging modality to study this hypothesis. We sought to correlate the relationship between acute bouts of ultra endurance exercise leading to cardiac biomarkers elevation and the presence of myocardial inflammation and fibrosis using CMR.Methods: 17 recreation athletes (33.5 +/- 6.5 years) were studied before and after a marathon run with troponin, NTproBNP, and CMR. Specific imaging parameters to look for inflammation included T2 weighted images, and T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA to detect myocardial hyperemia secondary to inflammation. Late gadolinium imaging was performed (LGE) to detect any focal regions of replacement fibrosis.Results: Eleven of the 17 participant had elevations of TnI above levels of cut off for myocardial infarction 6 hrs after the marathon (0.075 +/- 0.02, p = 0.007). Left ventricular volumes were reduced post marathon and a small increase in ejection fraction was noted (64 +/- 1% pre, 67 +/- 1.2% post, P = 0.014). Right ventricular volumes, stroke volume, and ejection fraction were unchanged post marathon. No athlete fulfilled criteria for myocardial inflammation based on current criteria. No regions of focal fibrosis were seen in any of the participants.Conclusion: Exercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis

Quantitative analysis of late gadolinium enhancement in hypertrophic cardiomyopathy: comparison of diagnostic performance in myocardial fibrosis between gadobutrol and gadopentetate dimeglumine

The purpose of this study was to compare different semi-automated late gadolinium enhancement (LGE) quantification techniques using gadobutrol and gadopentetate dimeglumine contrast agents with regard to the diagnosis of fibrotic myocardium in patients with hypertrophic cardiomyopathy (HCM). Thirty patients with HCM underwent two cardiac MRI protocols with use of gadobutrol and gadopentetate dimeglumine. Contrast-tonoise ratio (CNR) between LGE area and remote myocardium (CNRremote), between LGE area and left ventricular blood pool (CNRpool), and signal-to-noise ratio (SNR) in LGE were compared. The presence and quantity of LGE were determined by visual assessment. With signal threshold versus reference mean (STRM) based thresholds of 2 SD, 5 SD, and 6 SD above the mean signal intensity (SI) of reference myocardium, the full-width at half-maximum (FWHM) technique was used. The volume and segments of the LGE area were compared between the two types of contrast agents. LGE was present in 26 of 30 (86.6%) patients in both protocols. The CNRremote of fibrotic myocardium in gadobutrol and gadopentetate dimeglumine agents was 26.82 ± 14.24 and 21.46 ± 10.59, respectively (P &lt; 0.05). The CNRpool was significantly higher in gadobutrol (9.32 ± 7.64 vs. 6.39 ± 6.11, P &lt; 0.05). The SNR was higher in gadobutrol (33.36 ± 14.35 vs. 27.53 ± 10.91, P &lt; 0.05). The volume of scar size in MR images acquired with gadobutrol were significantly higher than those with gadopentetate dimeglumine (P &lt; 0.05), and the STRM of 5 SD technique showed the greatest agreement with visual assessment (ICC = 0.99) in both examinations. There was no significant difference in fibrotic segments of the fibrotic myocardium in the LGE area (P &lt; 0.05). This study proved that the Gadobutrol was an effective contrast agent for LGE imaging with superior delineation of fibrotic myocardium as compared to gadopentetate dimeglumine. The 5 SD technique yields the closest approximation of the extent of LGE identified by visual assessment