Combination Of Perfusion Research Articles

PD31-10 PRODUCTION OF VASCULARIZED FUNCTIONAL ORGAN CONSTRUCTS WITH LONG-TERM SURVIVAL

You have accessJournal of UrologyCME1 Apr 2023PD31-10 PRODUCTION OF VASCULARIZED FUNCTIONAL ORGAN CONSTRUCTS WITH LONG-TERM SURVIVAL Kelsey Willson, Sang Jin Lee, Young-Wook Moon, John Jackson, Colin Bishop, James Yoo, and Anthony Atala Kelsey WillsonKelsey Willson More articles by this author , Sang Jin LeeSang Jin Lee More articles by this author , Young-Wook MoonYoung-Wook Moon More articles by this author , John JacksonJohn Jackson More articles by this author , Colin BishopColin Bishop More articles by this author , James YooJames Yoo More articles by this author , and Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003324.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Developing large vascularized tissue constructs that can maintain long-term is an ongoing challenge. A strategy that has been gaining much attention is to bioengineer prevascularize tissue constructs that allow for immediate perfusion. We present the development of a large vascularized functional human liver construct that can be maintained for 30 days with high viability METHODS: Vascularized human liver tissue constructs of 1.5 cm in diameter and 6 cm in length were fabricated using an extrusion-based 3D printing system, seeded with hepatocytes (HepG2) in bulk hydrogel (alginate) and human umbilical vein endothelial cells (HUVECs) within the vascular channels. The alginate/HepG2 mixture was placed into a mold. A sacrificial gel (calcium chloride/HUVECs) was used to create vessels. Post printing, the samples were cured using calcium chloride and incubated at 37°C to liquefy the sacrificial gel. The liver tissue constructs were maintained in a media bath for 4 days, followed by media perfusion for 30 days using a peristaltic pump. The tissue samples were removed every 10 days and analyzed for cellular viability and biochemical functionality (albumin/bilirubin production). Immunohistochemistry was used to confirm the location of hepatocytes and endothelial cells. RESULTS: Alginate and calcium chloride was successfully used to fabricate constructs patterned with internal vascular channels running the entire length of the construct. The final constructs were cylindrical and maintained their structural integrity. The liver tissue samples showed high viability following fabrication and maintained a greater than 94 percent viability throughout the 30-day time point. The liver tissue constructs produced albumin and bilirubin at levels comparable to human liver tissue (assayed at 10, 20, and 30 days). In the retrieved constructs endothelial cells were identified on the vascular channel walls surrounded by hepatocytes in the hydrogel. CONCLUSIONS: We have successfully created large vascularized liver tissue constructs patterned with hollow channels using 3D bioprinting. The combination of perfusion and internal channels maintained high viability for 30 days. The liver tissue constructs produced albumin and bilirubin levels comparable to human liver tissue. This is a major step towards creating large vascularized functional liver tissue constructs that could be used for translational applications. Source of Funding: This work is a winner of NASA’s Vascular Tissue Challenge contest. The authors thank NASA for supporting this work in a zero-gravity environment on the International Space Station © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e904 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kelsey Willson More articles by this author Sang Jin Lee More articles by this author Young-Wook Moon More articles by this author John Jackson More articles by this author Colin Bishop More articles by this author James Yoo More articles by this author Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...

Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons.

As life expectancy increases, the population experiences progressive ageing. Ageing, in turn, is connected to an increase in bone-related diseases (i.e., osteoporosis and increased risk of fractures). Hence, the search for new approaches to study the occurrence of bone-related diseases and to develop new drugs for their prevention and treatment becomes more pressing. However, to date, a reliable in vitro model that can fully recapitulate the characteristics of bone tissue, either in physiological or altered conditions, is not available. Indeed, current methods for modelling normal and pathological bone are poor predictors of treatment outcomes in humans, as they fail to mimic the in vivo cellular microenvironment and tissue complexity. Bone, in fact, is a dynamic network including differently specialized cells and the extracellular matrix, constantly subjected to external and internal stimuli. To this regard, perfused vascularized models are a novel field of investigation that can offer a new technological approach to overcome the limitations of traditional cell culture methods. It allows the combination of perfusion, mechanical and biochemical stimuli, biological cues, biomaterials (mimicking the extracellular matrix of bone), and multiple cell types. This review will discuss macro, milli, and microscale perfused devices designed to model bone structure and microenvironment, focusing on the role of perfusion and encompassing different degrees of complexity. These devices are a very first, though promising, step for the development of 3D in vitro platforms for preclinical screening of novel anabolic or anti-catabolic therapeutic approaches to improve bone health.

Prediction of Disease Free Survival in Laryngeal and Hypopharyngeal Cancers Using CT Perfusion and Radiomic Features: A Pilot Study.

(1) Purpose: The objective was to evaluate CT perfusion and radiomic features for prediction of one year disease free survival in laryngeal and hypopharyngeal cancer. (2) Method and Materials: This retrospective study included pre and post therapy CT neck studies in 36 patients with laryngeal/hypopharyngeal cancer. Tumor contouring was performed semi-autonomously by the computer and manually by two radiologists. Twenty-six radiomic features including morphological and gray-level features were extracted by an internally developed and validated computer-aided image analysis system. The five perfusion features analyzed included permeability surface area product (PS), blood flow (flow), blood volume (BV), mean transit time (MTT), and time-to-maximum (Tmax). One year persistent/recurrent disease data were obtained following the final treatment of definitive chemoradiation or after total laryngectomy. We performed a two-loop leave-one-out feature selection and linear discriminant analysis classifier with generation of receiver operating characteristic (ROC) curves and confidence intervals (CI). (3) Results: 10 patients (28%) had recurrence/persistent disease at 1 year. For prediction, the change in blood flow demonstrated a training AUC of 0.68 (CI 0.47–0.85) and testing AUC of 0.66 (CI 0.47–0.85). The best features selected were a combination of perfusion and radiomic features including blood flow and computer-estimated percent volume changes-training AUC of 0.68 (CI 0.5–0.85) and testing AUC of 0.69 (CI 0.5–0.85). The laryngoscopic percent change in volume was a poor predictor with a testing AUC of 0.4 (CI 0.16–0.57). (4) Conclusions: A combination of CT perfusion and radiomic features are potential predictors of one-year disease free survival in laryngeal and hypopharyngeal cancer patients.

Multimodality imaging in takotsubo syndrome: a joint consensus document of the European Association of Cardiovascular Imaging (EACVI) and the Japanese Society of Echocardiography (JSE)

Takotsubo syndrome (TTS) is a complex and still poorly recognized heart disease with a wide spectrum of possible clinical presentations. Despite its reversibility, it is associated with serious adverse in-hospital events and high complication rates during follow-up. Multimodality imaging is helpful for establishing the diagnosis, guiding therapy, and stratifying prognosis of TTS patients in both the acute and post-acute phase. Echocardiography plays a key role, particularly in the acute care setting, allowing for the assessment of left ventricular (LV) systolic and diastolic function and the identification of the typical apical-midventricular ballooning pattern, as well as the circumferential pattern of wall motion abnormalities. It is also useful in the early detection of complications (i.e. LV outflow tract obstruction, mitral regurgitation, right ventricular involvement, LV thrombi, and pericardial effusion) and monitoring of systolic function recovery. Left ventriculography allows the evaluation of LV function and morphology, identifying the typical TTS patterns when echocardiography is not available or wall motion abnormalities cannot be properly assessed with ultrasound. Cardiac magnetic resonance provides a more comprehensive depiction of cardiac morphology and function and tissue characterization and offers additional value to other imaging modalities for differential diagnosis (myocardial infarction and myocarditis). Coronary computed tomography angiography has a substantial role in the diagnostic workup of patients with acute chest pain and a doubtful TTS diagnosis to rule out other medical conditions. It can be considered as a non-invasive appropriate alternative to coronary angiography in several clinical scenarios. Although the role of nuclear imaging in TTS has not yet been well established, the combination of perfusion and metabolic imaging may provide useful information on myocardial function in both the acute and post-acutephase.

Multimodality imaging in takotsubo syndrome: a joint consensus document of the European Association of Cardiovascular Imaging (EACVI) and the Japanese Society of Echocardiography (JSE).

Takotsubo syndrome (TTS) is a complex and still poorly recognized heart disease with a wide spectrum of possible clinical presentations. Despite its reversibility, it is associated with serious adverse in-hospital events and high complication rates during follow-up. Multimodality imaging is helpful for establishing the diagnosis, guiding therapy, and stratifying prognosis of TTS patients in both the acute and post-acute phase. Echocardiography plays a key role, particularly in the acute care setting, allowing for the assessment of left ventricular (LV) systolic and diastolic function and the identification of the typical apical-midventricular ballooning pattern, as well as the circumferential pattern of wall motion abnormalities. It is also useful in the early detection of complications (i.e. LV outflow tract obstruction, mitral regurgitation, right ventricular involvement, LV thrombi, and pericardial effusion) and monitoring of systolic function recovery. Left ventriculography allows the evaluation of LV function and morphology, identifying the typical TTS patterns when echocardiography is not available or wall motion abnormalities cannot be properly assessed with ultrasound. Cardiac magnetic resonance provides a more comprehensive depiction of cardiac morphology and function and tissue characterization and offers additional value to other imaging modalities for differential diagnosis (myocardial infarction and myocarditis). Coronary computed tomography angiography has a substantial role in the diagnostic workup of patients with acute chest pain and a doubtful TTS diagnosis to rule out other medical conditions. It can be considered as a non-invasive appropriate alternative to coronary angiography in several clinical scenarios. Although the role of nuclear imaging in TTS has not yet been well established, the combination of perfusion and metabolic imaging may provide useful information on myocardial function in both the acute and post-acute phase.

Enhancing all-in-one bioreactors by combining interstitial perfusion, electrical stimulation, on-line monitoring and testing within a single chamber for cardiac constructs

Tissue engineering strategies have been extensively exploited to generate functional cardiac patches. To maintain cardiac functionality in vitro, bioreactors have been designed to provide perfusion and electrical stimulation, alone or combined. However, due to several design limitations the integration of optical systems to assess cardiac maturation level is still missing within these platforms. Here we present a bioreactor culture chamber that provides 3D cardiac constructs with a bidirectional interstitial perfusion and biomimetic electrical stimulation, allowing direct cellular optical monitoring and contractility test. The chamber design was optimized through finite element models to house an innovative scaffold anchoring system to hold and to release it for the evaluation of tissue maturation and functionality by contractility tests. Neonatal rat cardiac fibroblasts subjected to a combined perfusion and electrical stimulation showed positive cell viability over time. Neonatal rat cardiomyocytes were successfully monitored for the entire culture period to assess their functionality. The combination of perfusion and electrical stimulation enhanced patch maturation, as evidenced by the higher contractility, the enhanced beating properties and the increased level of cardiac protein expression. This new multifunctional bioreactor provides a relevant biomimetic environment allowing for independently culturing, real-time monitoring and testing up to 18 separated patches.

Whole Cardiac Tissue Bioscaffolds.

Bioscaffolds serve as structures for cells in building complex tissues and full organs including heart. Decellularizing cardiac tissue results in cell-free extracellular matrix (ECM) that can be used as a cardiac tissue bioscaffold. The field of whole-heart tissue engineering has been revolutionized since the 2008 publication of the first perfusion-decellularized whole heart, and since then, studies have shown how decellularized cardiac tissue retains its native architecture and biochemistry following recellularization. Chemical, enzymatic, and physical decellularization methods preserve the ECM to varying degrees with the widely accepted standard of less than 50 ng/mg of double-stranded DNA present in decellularized ECM. Following decellularization, replacement of cells occurs via recellularization: seeding cells into the decellularized ECM structure either via perfusion of cells into the vascular conduits, injection into parenchyma, or a combination of perfusion and injection. Endothelial cells are often perfused through existing vessel conduits to provide an endothelial lining of the vasculature, with cardiomyocytes and other parenchymal cells injected into the myocardium of decellularized ECM bioscaffolds. Uniform cell density and cell retention throughout the bioscaffold still needs to be addressed in larger animal models of the whole heart. Generating the necessary cell numbers and types remains a challenge. Still, recellularized cardiac tissue bioscaffolds offer therapeutic solutions to heart failure, heart valve replacement, and acute myocardial infarction. New technologies allow for decellularized ECM to be bioprinted into cardiac bioscaffolds or formed into a cardiac hydrogel patch. This chapter reviews the advances made in decellularization and recellularization of cardiac ECM bioscaffolds with a discussion of the potential clinical applications of ECM bioscaffolds.

Optical coherence tomography angiography enhances the detection of optic nerve damage in multiple sclerosis

BackgroundQuantitative assessment of optic nerve damage is important in the evaluation of optic neuritis (ON) and multiple sclerosis (MS).ObjectiveTo detect optic nerve damage using optical coherence tomography (OCT) and OCT...

Quantification of fluid shear stress in bone tissue engineering scaffolds with spherical and cubical pore architectures.

Recent studies have shown that mechanical stimulation, in the form of fluid perfusion and mechanical compression, can enhance osteogenic differentiation of mesenchymal stem cells and bone cells within tissue engineering scaffolds in vitro. The precise nature of mechanical stimulation within tissue engineering scaffolds is not only dictated by the exogenously applied loading regime, but also depends on the geometric features of the scaffold, in particular architecture, pore size and porosity. However, the precise contribution of each geometric feature towards the resulting mechanical stimulation within a scaffold is difficult to characterise due to the wide range of interacting parameters. In this study, we have applied a fluid-structure interaction model to investigate the role of scaffold geometry (architecture, pore size and porosity) on pore wall shear stress (WSS) under a range of different loading scenarios: fluid perfusion, mechanical compression and a combination of perfusion and compression. It is found that scaffold geometry (spherical and cubical pores), in particular the pore size, has a significant influence on the stimulation within scaffolds. Furthermore, we observed an amplified WSS within scaffolds under a combination of fluid perfusion and mechanical compression, which exceeded that caused by individual fluid perfusion or mechanical compression approximately threefold. By conducting this comprehensive parametric variation study, an expression was generated to allow the design and optimisation of 3D TE scaffolds and inform experimental loading regimes so that a desired level of mechanical stimulation, in terms of WSS is generated within the scaffold.

Decellularization of a Fasciocutaneous Flap for Use as a Perfusable Scaffold

The aim of the current study was to determine whether a rat fasciocutaneous flap could be decellularized using detergent perfusion and/or agitation methods while preserving the integrity of the extracellular matrix and circulatory networks. Superficial inferior epigastric arterial flaps of 50 rats were randomly divided into the following 5 groups: (1) normal; (2) agitation in sodium dodecyl sulfate (SDS) for 72 hours (72h-AG); (3) perfusion and agitation with SDS for 12 hours (12h-PE-AG); (4) perfusion and agitation with SDS for 24 hours (24h-PE-AG); and (5) perfusion and agitation with SDS for 72 hours (72h-PE-AG). These flaps were evaluated by gross morphology, histology, integrity of the microcirculatory networks, and DNA quantification. The DNA content of the normal flap was 1.53 μg/mg. The decellularized flaps had significantly reduced DNA contents: 72h-AG (0.55 μg/mg), 12h-PE-AG (0.52 μg/mg), 24h-PE-AG (0.23 μg/mg), and 72h-PE-AG (0.17 μg/mg). The DNA contents in both the 24h-PE-AG and 72h-PE-AG groups were significantly less than that of 72h-AG and 12h-PE-AG groups. These findings were confirmed by histology and gross morphology. The integrity of the extracellular matrix and vascular system was preserved as measured by collagen and elastin stains in the 4 decellularized groups. Despite the histological appearance of vessel integrity, none of the flaps maintained physiologic vascular integrity by closed-loop circulation. A combination of perfusion and agitation for 24 hours or longer effectively decellularized the fasciocutaneous portion of composite tissue flaps and removed DNA content from the flap in our rat model with well-preserved vascular structure. This combined technique was superior to agitation alone. However, closed-loop circulation could not be preserved after decellularization with perfusion and/or agitation methods.

Multiscale fluid-structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold.

Recent studies have shown that mechanical stimulation, by means of flow perfusion and mechanical compression (or stretching), enhances osteogenic differentiation of mesenchymal stem cells and bone cells within biomaterial scaffolds in vitro. However, the precise mechanisms by which such stimulation enhances bone regeneration is not yet fully understood. Previous computational studies have sought to characterise the mechanical stimulation on cells within biomaterial scaffolds using either computational fluid dynamics or finite element (FE) approaches. However, the physical environment within a scaffold under perfusion is extremely complex and requires a multiscale and multiphysics approach to study the mechanical stimulation of cells. In this study, we seek to determine the mechanical stimulation of osteoblasts seeded in a biomaterial scaffold under flow perfusion and mechanical compression using multiscale modelling by two-way fluid-structure interaction and FE approaches. The mechanical stimulation, in terms of wall shear stress (WSS) and strain in osteoblasts, is quantified at different locations within the scaffold for cells of different attachment morphologies (attached, bridged). The results show that 75.4 % of scaffold surface has a WSS of 0.1-10 mPa, which indicates the likelihood of bone cell differentiation at these locations. For attached and bridged osteoblasts, the maximum strains are 397 and 177,200 με, respectively. Additionally, the results from mechanical compression show that attached cells are more stimulated (maximum strain = 22,600 με) than bridged cells (maximum strain = 10.000 με)Such information is important for understanding the biological response of osteoblasts under in vitro stimulation. Finally, a combination of perfusion and compression of a tissue engineering scaffold is suggested for osteogenic differentiation.

Improving Embryonic Stem Cell Expansion through the Combination of Perfusion and Bioprocess Model Design

BackgroundHigh proliferative and differentiation capacity renders embryonic stem cells (ESCs) a promising cell source for tissue engineering and cell-based therapies. Harnessing their potential, however, requires well-designed, efficient and reproducible expansion and differentiation protocols as well as avoiding hazardous by-products, such as teratoma formation. Traditional, standard culture methodologies are fragmented and limited in their fed-batch feeding strategies that afford a sub-optimal environment for cellular metabolism. Herein, we investigate the impact of metabolic stress as a result of inefficient feeding utilizing a novel perfusion bioreactor and a mathematical model to achieve bioprocess improvement.Methodology/Principal FindingsTo characterize nutritional requirements, the expansion of undifferentiated murine ESCs (mESCs) encapsulated in hydrogels was performed in batch and perfusion cultures using bioreactors. Despite sufficient nutrient and growth factor provision, the accumulation of inhibitory metabolites resulted in the unscheduled differentiation of mESCs and a decline in their cell numbers in the batch cultures. In contrast, perfusion cultures maintained metabolite concentration below toxic levels, resulting in the robust expansion (>16-fold) of high quality ‘naïve’ mESCs within 4 days. A multi-scale mathematical model describing population segregated growth kinetics, metabolism and the expression of selected pluripotency (‘stemness’) genes was implemented to maximize information from available experimental data. A global sensitivity analysis (GSA) was employed that identified significant (6/29) model parameters and enabled model validation. Predicting the preferential propagation of undifferentiated ESCs in perfusion culture conditions demonstrates synchrony between theory and experiment.Conclusions/SignificanceThe limitations of batch culture highlight the importance of cellular metabolism in maintaining pluripotency, which necessitates the design of suitable ESC bioprocesses. We propose a novel investigational framework that integrates a novel perfusion culture platform (controlled metabolic conditions) with mathematical modeling (information maximization) to enhance ESC bioprocess productivity and facilitate bioprocess optimization.

Intermediate-Term Prognostic Value of Reversible Perfusion Deficit Diagnosed by Adenosine CMR: A Prospective Follow-Up Study in a Consecutive Patient Population

The aim of this study was to assess the hypothesis that cardiac magnetic resonance (CMR) myocardial perfusion imaging can provide incremental prognostic value over other risk factors regarding the prediction of major cardiovascular events in a large, consecutive, and thereby unselected population of patients presenting with stable angina pectoris. Recently, it has been shown that CMR provides good short-term prognosis in patients with stable coronary heart disease. Reversible myocardial ischemia can be assessed using a combination of perfusion and late gadolinium enhancement imaging. Data concerning intermediate-term prognostic information, especially on major clinical endpoints such as cardiac death or myocardial infarction, are limited. From 2003 to 2007, consecutive patients with stable angina pectoris who underwent adenosine perfusion CMR were enrolled unless they met the predefined exclusion criteria. Myocardial perfusion imaging by adenosine stress and late gadolinium enhancement was assessed using a 1.5-T whole-body CMR scanner. Follow-up information concerning the combined endpoint of cardiac death, nonfatal myocardial infarction, and stroke was obtained from patients, general practitioners, or treating hospitals, respectively. In our study, 1,229 consecutive patients were enrolled. The mean follow-up period was 4.2 ± 2.1 years. During this time, 88 primary endpoints occurred. In patients with reversible perfusion deficits, significantly more cardiac deaths (p < 0.0001) and nonfatal myocardial infarctions (p = 0.001) were observed than in the control group. On multivariate analysis, reversible perfusion deficit was the strongest independent predictor for an event, with a 3-fold increased risk. Moreover, the absence of a perfusion deficit was shown to exhibit high negative predictive value. Adenosine perfusion CMR provides excellent risk stratification and intermediate-term prognostic value in patients with stable coronary artery disease. The presence of a myocardial perfusion deficit is an incremental prognostic risk factor over other risk factors.

Spatial regulation of human mesenchymal stem cell differentiation in engineered osteochondral constructs: effects of pre-differentiation, soluble factors and medium perfusion

The objective of the study was to investigate the combined effects of three sets of regulatory factors: cell pre-differentiation, soluble factors and medium perfusion on spatial control of human mesenchymal stem cell (hMSC) differentiation into cells forming the cartilaginous and bone regions in engineered osteochondral constructs. Bone-marrow derived hMSCs were expanded in their undifferentiated state (UD) or pre-differentiated (PD) in monolayer culture, seeded into biphasic constructs by interfacing agarose gels and bone scaffolds and cultured for 5 weeks either statically (S) or in a bioreactor (BR) with perfusion of medium through the bone region. Each culture system was operated with medium containing either chondrogenic supplements (C) or a cocktail (Ck) of chondrogenic and osteogenic supplements. The formation of engineered cartilage in the gel region was most enhanced by using undifferentiated cells and chondrogenic medium, whereas the cartilaginous properties were negatively affected by using pre-differentiated cells or the combination of perfusion and cocktail medium. The formation of engineered bone in the porous scaffold region was most enhanced by using pre-differentiated cells, perfusion and cocktail medium. Perfusion also enhanced the integration of bone and cartilage regions. (1) Pre-differentiation of hMSCs before seeding on scaffold was beneficial for bone but not for cartilage formation. (2) The combination of medium perfusion and cocktail medium inhibited chondrogenesis of hMSCs. (3) Perfusion improved the cell and matrix distribution in the bone region and augmented the integration at the bone-cartilage interface. (4) Osteochondral grafts can be engineered by differentially regulating the culture conditions in the two regions of the scaffold seeded with hMSCs (hydrogel for cartilage, perfused porous scaffold for bone).

Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease

There have been limited data regarding the value of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the detection of left main coronary artery disease (CAD). We studied 101 patients with angiographic left main CAD (> or = 50% stenosis) and no prior myocardial infarction or coronary revascularization who underwent gated exercise or adenosine stress technetium 99m sestamibi SPECT MPI. By perfusion assessment alone, high-risk disease with moderate to severe defects (> 10% myocardium at stress) was identified in only 56% of patients visually and 59% quantitatively. Absence of significant perfusion defect (> or = 5% myocardium) was seen in 13% of patients visually and 15% quantitatively. However, by combining visual perfusion data and nonperfusion variables, especially transient ischemic dilation, 83% of patients were identified as high risk. The findings of this study demonstrate that assessment of perfusion data alone by visual or quantitative SPECT MPI analysis underestimates the magnitude of left main CAD. The combination of perfusion and nonperfusion abnormalities on gated MPI identifies high risk in most patients with left main CAD.

The added value of ECG‐gating for the diagnosis of myocardial infarction using myocardial perfusion scintigraphy and artificial neural networks

To assess the value of ECG-gating for the diagnosis of myocardial infarction using myocardial perfusion scintigraphy (MPS) and an artificial neural network. A total of 422 patients referred for MPS were studied using a one day (99m)Tc-tetrofosmin protocol. Adenosine stress combined with submaximal dynamic exercise was used. The images were interpreted by one of three experienced clinicians and these interpretations regarding the presence or absence of myocardial infarction were used as the standard. A fully automated method using artificial neural networks was compared with the clinical interpretation. Either perfusion data alone or a combination of perfusion and function from ECG-gated images were used as input to different artificial neural networks. After a training session, the two types of neural networks were evaluated in separate test groups using an eightfold cross-validation procedure. The neural networks trained with both perfusion and ECG-gated images had a 4-7% higher specificity compared with the corresponding networks using perfusion data only, in four of five segments compared at the same level of sensitivity. The greatest improvement in specificity, from 70% to 77%, was seen in the inferior segment. In the septal and lateral segments the specificity rose from 73% to 77% and from 81% to 85%, respectively. In the anterior segment, the increase in specificity from 93% to 94% by adding functional data was not significant. The addition of functional information from ECG-gated MPS is of value for the diagnosis of myocardial infarction using an automated method of interpreting myocardial perfusion images.

Myocardial viability in patients with ischemic cardiomyopathy— evaluation by 3-D integration of myocardial scintigraphic data—and coronary angiographic data

Purpose To determine the prevalence of viable myocardium in patients with ischemic cardiomyopathy and, to evaluate the value of three-dimensional (3-D) fusion imaging of myocardial scintigraphic and angiographic data to assign coronary artery lesions to the corresponding viable and nonviable myocardial territory. Procedures In 105 patients, the combination of perfusion and metabolic imaging with 201thallium ( 201TI) single-photon emission computed tomography (SPECT) and 2-deoxy-2-[ 18F]fluoro-D-glucose (FDG) positron emission tomography (PET) determined viability in dysfunctional myocardium. In addition, the value of 3-D scintigraphic fusion imaging was assessed in these patients. Results Based on the presence of viable dysfunctional myocardium, 54% of patients with ischemic cardiomyopathy may be considered for coronary revascularization. In 31 of 105 patients, the 3-D fusion imaging was estimated to be helpful in the diagnostic and interpretative process. Conclusion In patients with end-stage coronary artery disease scintigraphic imaging is most important in the decision-making process. Three-dimensional fusion imaging may add important information in approximately 30% of these patients.

Tissue Viability Thresholds in Acute Stroke

Tissue Viability Thresholds in Acute Stroke

Assessment of myocardial perfusion using multisection first-pass MRI and color-coded parameter maps:: A comparison to 99mTc Sesta MIBI SPECT and systolic myocardial wall thickening analysis

The most recently reported magnetic resonance first-pass myocardial perfusion studies were restricted to single slice imaging or a data analysis based on interactively placed regions of interest. This study was designed to investigate a new saturation recovery TurboFLASH sequence for multisection myocardial perfusion imaging and to develop a pixel-based software tool to calculate qualitative perfusion parameters. The findings of perfusion imaging were compared to percent systolic myocardial wall thickening analysis and 99mTc Sesta MIBI SPECT. Six healthy volunteers and twelve patients with proven coronary artery disease (CAD) or chronic myocardial infarction were examined. Diagnostic images were acquired for all volunteers and patients with the multisection saturation recovery TurboFLASH sequence. Perfusion defects could be visualized on parameter maps for signal intensity increase over baseline and signal intensity upslope. Sensitivity and specificity were 76.9% and 97.1% for first-pass perfusion MRI, and respectively 84.6% and 94.3% for CINE imaging. All perfusion defects determined with 99mTc Sesta MIBI SPECT were identified by the combined analysis of myocardial perfusion and wall thickening. The presented software demonstrated a pixel-based analysis of first-pass perfusion studies and simplified image interpretation in a clinical setting. The combination of perfusion and wall motion imaging provided complementary information for the treatment of patients suffering from CAD.

RADIONUCLIDE VENTRICULAR FUNCTION ANALYSIS

The information available from ventricular function studies is important in the management of patients with cardiovascular disease. Radionuclide measurements of ventricular function are closely related to the presence and extent of myocardial damage secondary to various etiologies. The two most commonly used techniques to assess ventricular function are the first-pass radionuclide angiocardiogram and the equilibrium radionuclide angiogram. The first-pass radionuclide angiocardiographic technique assesses function at the time of the bolus administration of the radiotracer. The cardiac blood pool imaging technique has the advantage of being able to assess function hours after tracer administration. Both techniques have their own limitations and advantages. Several measurements can be obtained with radionuclide ventricular function analysis. The most important parameters obtained are the right and left ventricular EFs, wall motion analysis, intracardiac shunts, volumes, and diastolic function. Radionuclide ventricular function analysis can provide information beneficial to patient management in a variety of cardiac disorders including ischemic heart disease, valvular heart disease, and congenital heart disease. Radionuclide ventricular function measurements are well established, important determinants in patients with diagnosis and prognosis of cardiovascular disorders. New 99mTc-labeled radiopharmaceuticals are now available and permit the simultaneous measurement of myocardial perfusion and ventricular function. The combined perfusion and function studies obtained during a single tracer administration provide a large amount of information important to the management of patients with cardiovascular disease. The combination of perfusion and functional measurements may improve the prognostic evaluation of patients with cardiovascular disease.