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2.
J Cardiovasc Magn Reson ; 25(1): 38, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37394485

ABSTRACT

INTRODUCTION: The use of cardiovascular magnetic resonance (CMR) for diagnosis and management of a broad range of cardiac and vascular conditions has quickly expanded worldwide. It is essential to understand how CMR is utilized in different regions around the world and the potential practice differences between high-volume and low-volume centers. METHODS: CMR practitioners and developers from around the world were electronically surveyed by the Society for Cardiovascular Magnetic Resonance (SCMR) twice, requesting data from 2017. Both surveys were carefully merged, and the data were curated professionally by a data expert using cross-references in key questions and the specific media access control IP address. According to the United Nations classification, responses were analyzed by region and country and interpreted in the context of practice volumes and demography. RESULTS: From 70 countries and regions, 1092 individual responses were included. CMR was performed more often in academic (695/1014, 69%) and hospital settings (522/606, 86%), with adult cardiologists being the primary referring providers (680/818, 83%). Evaluation of cardiomyopathy was the top indication in high-volume and low-volume centers (p = 0.06). High-volume centers were significantly more likely to list evaluation of ischemic heart disease (e.g., stress CMR) as a primary indicator compared to low-volume centers (p < 0.001), while viability assessment was more commonly listed as a primary referral reason in low-volume centers (p = 0.001). Both developed and developing countries noted cost and competing technologies as top barriers to CMR growth. Access to scanners was listed as the most common barrier in developed countries (30% of responders), while lack of training (22% of responders) was the most common barrier in developing countries. CONCLUSION: This is the most extensive global assessment of CMR practice to date and provides insights from different regions worldwide. We identified CMR as heavily hospital-based, with referral volumes driven primarily by adult cardiology. Indications for CMR utilization varied by center volume. Efforts to improve the adoption and utilization of CMR should include growth beyond the traditional academic, hospital-based location and an emphasis on cardiomyopathy and viability assessment in community centers.


Subject(s)
Cardiology , Cardiomyopathies , Adult , Humans , Predictive Value of Tests , Magnetic Resonance Imaging , Cardiology/education , Magnetic Resonance Spectroscopy
3.
Sci Rep ; 13(1): 5229, 2023 03 30.
Article in English | MEDLINE | ID: mdl-36997599

ABSTRACT

Studies of the usefulness of transverse right ventricular (RV) shortening are limited. We retrospectively analyzed the CMR images of 67 patients (age: 50.8 ± 19.0 years; men: 53.7%; Control: n = 20, Overloaded RV (atrial septal defect): n = 15, Constricted RV (pericarditis): n = 17, Degenerated RV (arrhythmogenic right ventricular cardiomyopathy): n = 15) (all enrolled consecutively for each disease) in a single center. We defined RV longitudinal (fractional longitudinal change: FLC) and transverse (fractional transverse change: FTC) contraction parameters. We assessed the FTC/FLC (T/L) ratio on four-chamber cine CMR views and compared the four groups regarding the fractional parameters. FTC had a stronger correlation (R2 = 0.650; p < 0.001) with RV ejection fraction than that with FLC (R2 = 0.211; p < 0.001) in the linear regression analysis. Both FLC and FTC were significantly lower in the Degenerated RV and Constricted RV groups compared with those in the Control and Overloaded RV groups. The T/L ratio was significantly lower in the Degenerated RV group (p = 0.008), while the Overloaded RV (p = 0.986) and Constricted RV (p = 0.582) groups had preserved T/L ratios, compared with the Control group. Transverse shortening contributes to RV function more significantly compared with longitudinal contraction. Impaired T/L ratios may reflect RV myocardial degeneration. RV fractional parameters may help precisely understand RV dysfunction.


Subject(s)
Magnetic Resonance Imaging, Cine , Ventricular Dysfunction, Right , Male , Humans , Adult , Middle Aged , Aged , Magnetic Resonance Imaging, Cine/methods , Retrospective Studies , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology , Myocardium , Stroke Volume
4.
Colloids Surf B Biointerfaces ; 164: 42-49, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29413619

ABSTRACT

A hydrophilic amino compound, 4,7,10-trioxatridecane-1,13-diamine, has been utilized in several chemical and biochemical studies. Among previous applications is its use as a flexible and economical spacer molecule to increase the length between two moieties of interest, one of which may be a solid-phase interface. In this study, we immobilized this molecule on cotton fabrics and showed that this modified surface (DA) exhibited significant antibacterial activities in both Gram-negative bacteria and a Gram-positive bacterium. Studies on the structure-activity relationship revealed that additional chemical modifications on DA usually led to lowered antibacterial activities, emphasizing an importance of having free amino groups. Further investigation by fluorescence microscope indicated that this modified surface likely interfered with the membrane integrity of bacteria, leading to cell lysis. In addition, this scaffold was also tested for its biocompatibility with mouse fibroblast cells, and exerted no detrimental effect to the cell growth, highlighting its potential as a practical antibacterial surface modifier.


Subject(s)
Amines/chemistry , Anti-Bacterial Agents/pharmacology , Cotton Fiber , Hydrophobic and Hydrophilic Interactions , Tissue Scaffolds/chemistry , Animals , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Fibroblasts/cytology , Fibroblasts/drug effects , Materials Testing , Mice , Photoelectron Spectroscopy
5.
Heart Vessels ; 33(5): 513-520, 2018 May.
Article in English | MEDLINE | ID: mdl-29168014

ABSTRACT

Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging has demonstrated the capability of stratifying hypertrophic cardiomyopathy (HCM). Stress perfusion test of CMR can quantify myocardial perfusion reserve (MPR), but its clinical role is not determined. The purpose of this study was to investigate the relationship between MPR and LGE in patients with HCM. A total of 61 consecutive cases underwent complete evaluation with electrocardiography and CMR [cine imaging, coronary MR angiography (MRA), and stress perfusion testing with LGE]. HCM cases were diagnosed by the Japanese conventional guideline prior to this CMR study. Mild LVH was defined as more than 13 mm in maximum LV wall thickness at end diastole on the cine imaging of the CMR. MPR was calculated as the ratio of stress/rest myocardial blood flow using an intensity curve on the stress perfusion test. Cases with ischemic heart disease were excluded from the study based on clinical history and coronary MRA. There were 37 HCM and 24 mild LVH cases (average age: 60.5 ± 10.9 vs. 64.8 ± 10.8; male: 62.2 vs. 75.0%, respectively, non-significant). MPR in HCM was lower than in LVH (1.5 ± 0.5 vs. 2.2 ± 0.9, p < 0.001) and normal subjects (2.4 ± 0.9, p < 0.001). MPR in HCM with LGE (N = 34) was lower than in HCM without LGE (N = 3) (1.4 ± 0.5 vs. 2.1 ± 0.2, p = 0.014). Multiple regression analysis verified that LGE was the strongest predictor of MPR among multiple clinical parameters, including LVH, LV dysfunction (ejection fraction < 50%), and the presence of negative T wave (p < 0.001). MPR was impaired in HCM with LGE compared with HCM without LGE. The clinical role of MPR on CMR needs to be clarified by further research.


Subject(s)
Cardiomyopathy, Hypertrophic/diagnosis , Coronary Circulation/physiology , Electrocardiography , Gadolinium DTPA/pharmacology , Magnetic Resonance Imaging, Cine/methods , Myocardium/pathology , Cardiomyopathy, Hypertrophic/physiopathology , Contrast Media/pharmacology , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
6.
Intern Med ; 57(7): 975-978, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29269664

ABSTRACT

A 55-year-old man presented with dyspnea, edema, and appetite loss. He had undergone coronary artery bypass grafting 8 years previously. He had jugular venous distention and Kussmaul's sign. Contrast-enhanced cardiac magnetic resonance imaging (CMRI) demonstrated an intrapericardial mass compressing the right ventricular (RV) cavity. T1- and T2-weighted black-blood images showed a mass with heterogeneous high signal intensity and a thick and dark rim. The mass was considered to be a chronic hematoma. After pericardiotomy with surgical removal of the hematoma, CMRI showed the marked improvement of the RV function. Late intrapericardial hematoma is rare and CMRI is useful for making a differential diagnosis.


Subject(s)
Coronary Artery Bypass/adverse effects , Heart Ventricles/diagnostic imaging , Hematoma/diagnostic imaging , Hematoma/surgery , Heart Ventricles/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Treatment Outcome
7.
Diabetes Ther ; 8(4): 851-861, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28616806

ABSTRACT

INTRODUCTION: Epicardial fat (EF) was reported to be independently associated with cardiovascular disease regardless of obesity. We have previously reported that a sodium-glucose co-transporter-2 (SGLT2) inhibitor, luseogliflozin, reduces the EF volume (EFV) in parallel with the reduction of body weight in obese patients (BMI ≥25 kg/m2) with type 2 diabetes. However, it is unknown whether SGLT2 inhibitors could reduce EFV in non-obese patients (BMI <25 kg/m2) with type 2 diabetes. Therefore, we evaluated the effect of SGLT2 inhibitors on the EFV in non-obese type 2 diabetic patients with visceral obesity in this pilot study. METHODS: Nine of type 2 diabetic patients (mean age 66 ± 8 years; 33% female) with HbA1c 6.5-9.0%, body mass index (BMI, kg/m2) <25.0, and visceral fat area (VFA, cm2) ≥100 were enrolled. Participants were administered ipragliflozin 50 mg daily. EFV [median (interquartile range), cm3] was measured by magnetic resonance imaging. Primary endpoint was the change in EFV at 12 weeks. VFA and liver attenuation index (LAI), skeletal muscle index (SMI), and body fat (%) were also assessed at baseline and at 12 weeks. RESULTS: The EFV was significantly reduced from 102 (79-126) cm3 to 89 (66-109) cm3 by ipraglifrozin (p = 0.008). The body weight, BMI, HbA1c, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance, triglycerides, leptin, body fat, android, gynoid, and VFA were significantly reduced and high-density lipoprotein cholesterol was significantly increased by ipraglifrozin at 12 weeks, whereas SFA and LAI were unchanged. The change in EFV was significantly correlated with the change in BMI. CONCLUSIONS: A12-week intervention of ipragliflozin reduced the EFV in non-obese type 2 diabetic patients with visceral adiposity. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000019071. FUNDING: Astellas Pharma Inc. and the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

8.
Cardiovasc Diabetol ; 16(1): 32, 2017 03 03.
Article in English | MEDLINE | ID: mdl-28253918

ABSTRACT

BACKGROUND: Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV. METHODS: Type 2 diabetic patients with HbA1c 6.5-9.0% and body mass index (BMI, kg/m2) ≥25.0 were enrolled in this single arm pilot study. Participants were administered luseogliflozin 2.5 mg daily and the dosage was tolerated to be increased up to 5.0 mg daily. EFV [median (interquartile range), cm3] was measured by magnetic resonance imaging. Primary endpoint was the decrease in EFV at 12 weeks. Visceral fat area (VFA, cm2) and liver attenuation index (LAI) measured by the abdominal computed tomography, and skeletal muscle index (SMI) and body fat (%) measured by the whole body dual-energy X-ray absorptiometry were also determined at baseline and at 12 weeks. RESULTS: Nineteen patients (mean age: 55 ± 12 years; 26% female) completed this study. Luseogliflozin treatment significantly reduced EFV at 12 weeks [117 (96-136) to 111 (88-134), p = 0.048]. The body weight, BMI, systolic and diastolic blood pressure, HbA1c, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, SMI, and body fat were significantly reduced by luseogliflozin at 12 weeks. The reduction of EFV was significantly correlated with the reduction of C-reactive protein (r = 0.493, p = 0.019). Neither VFA nor LAI were significantly reduced by the luseogliflozin treatment. No severe adverse events were observed. CONCLUSIONS: Our data suggest that luseogliflozin could reduce the EFV in parallel with the improvement of systemic micro-inflammation and the reduction of body weight in Japanese patients with type 2 diabetes. The reduction of muscle mass after the administration of SGLT2 inhibitors may require a particular attention. Trial registration umin.ac.jp, UMIN000019072.


Subject(s)
Diabetes Mellitus, Type 2/diagnostic imaging , Diabetes Mellitus, Type 2/drug therapy , Intra-Abdominal Fat/diagnostic imaging , Pericardium/diagnostic imaging , Sorbitol/analogs & derivatives , Adipose Tissue/diagnostic imaging , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adult , Aged , Diabetes Mellitus, Type 2/blood , Female , Humans , Intra-Abdominal Fat/drug effects , Intra-Abdominal Fat/metabolism , Male , Middle Aged , Pericardium/drug effects , Pilot Projects , Sodium-Glucose Transporter 2/metabolism , Sorbitol/pharmacology , Sorbitol/therapeutic use
9.
PLoS One ; 10(12): e0145855, 2015.
Article in English | MEDLINE | ID: mdl-26720837

ABSTRACT

AIMS: The assessment of the distribution and activity of vessel wall inflammation is clinically important in patients with Takayasu arteritis. Magnetic resonance imaging (MRI) is a useful tool, but the clinical utility of late gadolinium enhancement (LGE) in Takayasu arteritis has yet to be determined. The aim of the present study was to evaluate the utility of LGE in assessing vessel wall inflammation and disease activity in Takayasu arteritis. METHODS AND RESULTS: We enrolled 49 patients with Takayasu arteritis who had undergone 1.5 T MRI. Patients were divided into Active (n = 19) and Inactive disease (n = 30) groups. The distribution of vessel wall inflammation using angiography and LGE was assessed by qualitative analysis. In 79% and 63% of patients in Active and Inactive groups, respectively, greater distribution of vessel wall inflammation was observed with LGE than with conventional angiography. MRI values of pre- and post-contrast signal-to-noise ratios (SNR), SNR increment (post-SNR minus pre-SNR), pre- and post-contrast contrast-to-noise ratios (CNR), and CNR increment (post-CNR minus pre-CNR) were evaluated at arterial wall sites with the highest signal intensity using quantitative analysis of post-contrast LGE images. No statistically significant differences in MRI parameters were observed between Active and Inactive groups. Contrast-enhanced MRI was unable to accurately detect active disease. CONCLUSION: Contrast-enhanced MRI has utility in detecting the distribution of vessel wall inflammation but has less utility in assessing disease activity in Takayasu arteritis.


Subject(s)
Contrast Media , Image Enhancement , Magnetic Resonance Imaging , Takayasu Arteritis/diagnosis , Adult , Aorta/pathology , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Angiography/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged , Observer Variation , Retrospective Studies , Signal-To-Noise Ratio , Takayasu Arteritis/pathology , Young Adult
10.
J Card Fail ; 21(4): 313-22, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25512195

ABSTRACT

BACKGROUND: Isolated cardiac sarcoidosis (iCS) is difficult to diagnose in patients without histologic evidence of sarcoidosis. We aimed to clarify the clinical characteristics of iCS, including imaging features on cardiac magnetic resonance imaging (MRI) and (18)F-fluoro-2-deoxyglucose positron-emission tomography/computerized tomography (FDG-PET/CT) scans. We also reviewed the therapeutic effect of corticosteroids and determined the long-term prognosis. METHODS AND RESULTS: We retrospectively reviewed 83 consecutive patients with suspicious CS from 1997 to 2013. Systemic sarcoidosis with CS (sCS, n = 30) and iCS (n = 11) were diagnosed according to clinical criteria. In iCS cases, sarcoidosis was not detected in any other organs. The clinical features did not significantly differ between sCS and iCS cases, except for ejection fraction, which was lower in iCS (P = .025). Nine sCS and 4 iCS cases showed late gadolinium enhancement, and the lesions tended to be on the epicardial side (76.9% P = .011) and septal wall (52.9% P < .001). The coefficient of variance for the myocardial standardized uptake value of FDG-PET/CT was higher in sCS (0.32 ± 0.13; n = 19) and iCS (0.32 ± 0.09; n = 7) than in control cases (n = 31; P < .001). B-Type natriuretic peptide level was improved after prednisolone treatment in both groups. Kaplan-Meier curve indicated that prognosis was not different between sCS and iCS cases. CONCLUSIONS: The clinical cardiac characteristics of iCS cases were similar to those of sCS. Cardiac MRI and FDG-PET, noninvasive imaging modalities, could be useful modalities to detect myocardial involvement in the cases with definite or suspected iCS.


Subject(s)
Cardiomyopathies/diagnosis , Fluorodeoxyglucose F18 , Magnetic Resonance Imaging, Cine/methods , Positron-Emission Tomography/methods , Sarcoidosis/diagnosis , Tomography, X-Ray Computed/methods , Aged , Female , Humans , Male , Middle Aged , Prognosis , Radiopharmaceuticals , Reproducibility of Results , Retrospective Studies
11.
Int Heart J ; 54(2): 119-22, 2013.
Article in English | MEDLINE | ID: mdl-23676374

ABSTRACT

Amniotic fluid embolism (AFE) is a rare but devastating complication of pregnancy. Acute circulatory failure and obstetric disseminated intravascular coagulopathy are often associated with AFE and lead to poor prognosis of this syndrome. Although many reports of AFE and its cardiopulmonary complications exist, their etiology remains unknown. Classically, it was believed that the fatal cardiopulmonary complication in AFE is due to acute and severe pulmonary hypertension caused by critical obstruction of the pulmonary vessels by embolized amniotic fluid. However, recent hypotheses are suggesting that anaphylactic reaction or a cytokine effect induced by amniotic fluid is the main pathophysiological mechanism. We report a case in which cardiac magnetic resonance imaging was performed at the chronic stage of AFE. Late gadolinium enhancement (LGE) was detected at the mid-wall of the left ventricle with no evidence of pulmonary hypertension. This finding suggests that the pathophysiological mechanism of severe cardiac complications in AFE may include direct left ventricular myocardial injury through an immune reaction or cytokine release, rather than pulmonary embolism.


Subject(s)
Embolism, Amniotic Fluid/etiology , Embolism, Amniotic Fluid/physiopathology , Heart/physiopathology , Myocardium/pathology , Adult , Embolism, Amniotic Fluid/pathology , Embolism, Amniotic Fluid/therapy , Female , Gadolinium , Humans , Magnetic Resonance Imaging , Pregnancy
12.
Heart Vessels ; 28(5): 596-605, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23014927

ABSTRACT

Although atrial natriuretic peptide (ANP) is widely used in patients with congestive heart failure (CHF), little is known about its effect on epicardial coronary arteries. Magnetic resonance imaging (MRI) enables precise measurement of coronary vasodilation and flow velocity. In this study, we examined the changes in epicardial coronary artery size and flow velocity in response to intravenous infusion of ANP or nitroglycerin (NTG) by using 3 T MRI in patients with CHF. The study cohort contained a total of 14 subjects: 8 patients with CHF and 6 healthy volunteers as controls, randomly divided into two groups: the ANP group (0.03 µg/kg/min) and the NTG group (0.3 µg/kg/min). Cross-sectional MR angiography and phase-contrast flow velocity of the right coronary artery in the same in-plane slice were obtained at the baseline, during drug infusion, and at two subsequent time points after stopping drug infusion. A significant increase was observed in the coronary cross-sectional area at 15 min after drug infusion in both groups compared with that at baseline; however, a late peak was observed at 15 min after stopping infusion in the ANP group. No significant differences were detected in the flow velocity in both groups. Furthermore, although NTG increased the heart rate, this change was not found in the ANP group. Coronary vasodilation and flow velocity can be measured simultaneously using 3 T MRI. Using this method, we showed that the effects of ANP on the coronary artery vasodilation and flow velocity were not inferior to those of NTG, with no significant alteration in heart rate.


Subject(s)
Atrial Natriuretic Factor/administration & dosage , Coronary Circulation/drug effects , Coronary Vessels/drug effects , Heart Failure/drug therapy , Magnetic Resonance Angiography , Nitroglycerin/administration & dosage , Vasodilation/drug effects , Vasodilator Agents/administration & dosage , Adult , Aged , Blood Flow Velocity/drug effects , Coronary Vessels/physiopathology , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Rate/drug effects , Humans , Infusions, Intravenous , Japan , Male , Middle Aged , Predictive Value of Tests , Time Factors , Treatment Outcome
13.
Mol Imaging ; 11(2): 126-34, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22469240

ABSTRACT

Macrophage infiltration is a prominent feature of abdominal aortic aneurysm (AAA) progression. We used a combined imaging approach with bioluminescence (BLI) and magnetic resonance imaging (MRI) to study macrophage homing and accumulation in experimental AAA disease. Murine AAAs were created via intra-aortic infusion of porcine pancreatic elastase. Mice were imaged over 14 days after injection of prepared peritoneal macrophages. For BLI, macrophages were from transgenic mice expressing luciferase. For MRI, macrophages were labeled with iron oxide particles. Macrophage accumulation during aneurysm progression was observed by in situ BLI and by in vivo 7T MRI. Mice were sacrificed after imaging for histologic analysis. In situ BLI (n  =  32) demonstrated high signal in the AAA by days 7 and 14, which correlated significantly with macrophage number and aortic diameter. In vivo 7T MRI (n  =  13) at day 14 demonstrated T2* signal loss in the AAA and not in sham mice. Immunohistochemistry and Prussian blue staining confirmed the presence of injected macrophages in the AAA. BLI and MRI provide complementary approaches to track macrophage homing and accumulation in experimental AAAs. Similar dual imaging strategies may aid the study of AAA biology and the evaluation of novel therapies.


Subject(s)
Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/pathology , Cell Movement , Luminescent Measurements/methods , Macrophages/pathology , Magnetic Resonance Imaging/methods , Animals , Ferric Compounds/metabolism , Ferrocyanides , Galectin 3/metabolism , Immunohistochemistry , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Staining and Labeling
14.
JACC Cardiovasc Imaging ; 4(6): 622-9, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21679897

ABSTRACT

OBJECTIVES: We investigated the association between physical activity and coronary vasodilation to nitroglycerin (NTG) in the ADVANCE (Atherosclerotic Disease, Vascular Function, and Genetic Epidemiology) cohort of older healthy subjects. BACKGROUND: Physical activity may exert its beneficial effects by augmenting coronary responsiveness to nitric oxide. The relationship between physical activity and coronary vasodilatory response to NTG, an exogenous nitric oxide donor, has not been studied in a community-based population with typical activity levels. METHODS: In 212 older adults (ages 60 to 72 years) without cardiovascular disease, we measured the coronary vasodilatory response to NTG using magnetic resonance angiography and physical activity using the Stanford Seven-Day Physical Activity Recall Questionnaire. The primary predictor measure was total physical activity (kcal/kg/day). The primary outcome measure was coronary vasodilatory response (percent increase of cross-sectional area post-NTG). RESULTS: Coronary vasodilation was 27.6% in more active subjects (>35 kcal/kg/day, e.g., 1 h of walking per day) compared to 18.9% in less active subjects (p=0.03). Regression analysis showed a significant positive correlation between coronary vasodilation and physical activity (p=0.003), with a slope (beta) of 1.2% per kcal/kg/day. This finding remained significant after adjustment for cardiac risk factors, coronary calcium, the use of vasoactive or statin medications, and analysis of physical activity by quintiles (p < 0.05). Coronary vasodilation was also associated with physical activity intensity (p = 0.03). CONCLUSIONS: In an asymptomatic, community-based cohort of older adults, increased coronary vasodilatory response was independently associated with greater physical activity, supporting the benefits of exercise on the order of 1 h of walking per day.


Subject(s)
Aging , Coronary Circulation , Coronary Vessels/physiology , Motor Activity , Vasodilation , Age Factors , Aged , California , Chi-Square Distribution , Coronary Circulation/drug effects , Coronary Vessels/drug effects , Cross-Sectional Studies , Female , Humans , Linear Models , Magnetic Resonance Angiography , Male , Middle Aged , Nitric Oxide Donors/administration & dosage , Nitroglycerin/administration & dosage , Surveys and Questionnaires , Vasodilation/drug effects , Vasodilator Agents/administration & dosage
15.
ACS Nano ; 5(4): 2493-502, 2011 Apr 26.
Article in English | MEDLINE | ID: mdl-21391720

ABSTRACT

Cage-like protein nanoparticles are promising platforms for cell- and tissue-specific targeted delivery of imaging and therapeutic agents. Here, we have successfully modified the 12 nm small heat shock protein from Methanococcus jannaschii (MjHsp) to detect atherosclerotic plaque lesions in a mouse model system. As macrophages are centrally involved in the initiation and progression of atherosclerosis, targeted imaging of macrophages is valuable to assess the biologic status of the blood vessel wall. LyP-1, a nine residue peptide, has been shown to target tumor-associated macrophages. Thus, LyP-1 was genetically incorporated onto the exterior surface of MjHsp, while a fluorescent molecule (Cy5.5) was conjugated on the interior cavity. This bioengineered protein cage, LyP-Hsp, exhibited enhanced affinity to macrophage in vitro. Furthermore, in vivo injection of LyP-Hsp allowed visualization of macrophage-rich murine carotid lesions by in situ and ex vivo fluorescence imaging. These results demonstrate the potential of LyP-1-conjugated protein cages as nanoscale platforms for delivery of imaging agents for the diagnosis of atherosclerosis.


Subject(s)
Macrophages/cytology , Nanoparticles , Peptide Fragments/chemistry , Peptides, Cyclic/chemistry , Proteins/chemistry , Vascular Diseases/pathology , Amino Acid Sequence , Animals , Cell Line , Chromatography, Gel , Flow Cytometry , Fluorescent Dyes/chemistry , Mice , Microscopy, Electron, Transmission , Models, Animal , Spectrometry, Fluorescence
16.
PLoS One ; 6(1): e14523, 2011 Jan 14.
Article in English | MEDLINE | ID: mdl-21264237

ABSTRACT

BACKGROUND: FeCo/graphitic-carbon nanocrystals (FeCo/GC) are biocompatible, high-relaxivity, multi-functional nanoparticles. Macrophages represent important cellular imaging targets for assessing vascular inflammation. We evaluated FeCo/GC for vascular macrophage uptake and imaging in vivo using fluorescence and MRI. METHODS AND RESULTS: Hyperlipidemic and diabetic mice underwent carotid ligation to produce a macrophage-rich vascular lesion. In situ and ex vivo fluorescence imaging were performed at 48 hours after intravenous injection of FeCo/GC conjugated to Cy5.5 (n = 8, 8 nmol of Cy5.5/mouse). Significant fluorescence signal from FeCo/GC-Cy5.5 was present in the ligated left carotid arteries, but not in the control (non-ligated) right carotid arteries or sham-operated carotid arteries (p = 0.03 for ligated vs. non-ligated). Serial in vivo 3T MRI was performed at 48 and 72 hours after intravenous FeCo/GC (n = 6, 270 µg Fe/mouse). Significant T2* signal loss from FeCo/GC was seen in ligated left carotid arteries, not in non-ligated controls (p = 0.03). Immunofluorescence staining showed colocalization of FeCo/GC and macrophages in ligated carotid arteries. CONCLUSIONS: FeCo/GC accumulates in vascular macrophages in vivo, allowing fluorescence and MR imaging. This multi-functional high-relaxivity nanoparticle platform provides a promising approach for cellular imaging of vascular inflammation.


Subject(s)
Biocompatible Materials/pharmacokinetics , Diagnostic Imaging/methods , Graphite/pharmacokinetics , Inflammation/pathology , Macrophages/metabolism , Nanoparticles , Animals , Biocompatible Materials/chemistry , Carotid Arteries , Cobalt , Contrast Media/chemistry , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Ferrous Compounds , Graphite/administration & dosage , Hyperlipidemias/metabolism , Hyperlipidemias/pathology , Inflammation/diagnosis , Magnetic Resonance Imaging , Mice , Nanoparticles/administration & dosage
17.
Mol Imaging Biol ; 13(6): 1061-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21057879

ABSTRACT

PURPOSE: Inflammation plays a critical role in atherosclerosis and is associated with upregulation of inducible nitric oxide synthase (iNOS). We studied bioluminescence imaging (BLI) to track iNOS gene expression in a murine model of vascular inflammation. PROCEDURES: Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in 18 iNOS-luc reporter mice. In vivo iNOS expression was imaged serially by BLI over 14 days, followed by in situ BLI and histology. RESULTS: BLI signal from ligated carotids increased over 14 days (9.7 ± 4.4 × 10(3 ) vs. 4.4 ± 1.7 × 10(3) photons/s/cm(2)/sr at baseline, p < 0.001 vs. baseline, p < 0.05 vs. sham controls). Histology confirmed substantial macrophage infiltration, with iNOS and luciferase expression, only in ligated left carotid arteries and not controls. CONCLUSIONS: BLI allows in vivo detection of iNOS expression in murine carotid lesions and may provide a valuable approach for monitoring vascular gene expression and inflammation in small animal models.


Subject(s)
Carotid Artery, Common/pathology , Gene Expression Regulation, Enzymologic , Imaging, Three-Dimensional/methods , Inflammation/enzymology , Inflammation/genetics , Luminescent Measurements/methods , Nitric Oxide Synthase Type II/genetics , Animals , Carotid Artery, Common/enzymology , Luciferases/metabolism , Macrophages , Mice , Nitric Oxide Synthase Type II/metabolism , Staining and Labeling
18.
Biomaterials ; 32(5): 1430-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21074263

ABSTRACT

Atherosclerosis is a leading cause of death worldwide. Macrophages are key components of vascular inflammation, which contributes to the development and complications of atherosclerosis. Ferritin, an iron storage and transport protein, has been found to accumulate in macrophages in human atherosclerotic plaques. We hypothesized that ferritin could serve as an intrinsic nano-platform to target delivery of imaging agents to vascular macrophages to detect high-risk atherosclerotic plaques. Here we show that engineered human ferritin protein cages, either conjugated to the fluorescent Cy5.5 molecule or encapsulating a magnetite nanoparticle, are taken up in vivo by macrophages in murine atherosclerotic carotid arteries and can be imaged by fluorescence and magnetic resonance imaging. These results indicate that human ferritin can serve as a nanoparticle platform to image vascular inflammation in vivo.


Subject(s)
Ferritins/chemistry , Macrophages/metabolism , Animals , Atherosclerosis/metabolism , Atherosclerosis/pathology , Carbocyanines/chemistry , Humans , Magnetic Resonance Imaging , Magnetite Nanoparticles/chemistry , Mice , Models, Theoretical , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/pathology
19.
J Am Coll Cardiol ; 55(24): 2762-8, 2010 Jun 15.
Article in English | MEDLINE | ID: mdl-20538171

ABSTRACT

OBJECTIVES: This study evaluates how characterization of tissue heterogeneity of myocardial infarction by cardiovascular magnetic resonance (CMR) is associated with cardiovascular events (CVE) in patients with ischemic cardiomyopathy (ICM). BACKGROUND: Prior studies demonstrated that the quantification of myocardial scar volume by CMR is superior to left ventricular end-diastolic volume, left ventricular end-systolic volume, and left ventricular ejection fraction (LVEF) in predicting future CVE in ICM patients. Evaluation of infarct heterogeneity by measuring infarct core and border zones through CMR might have a higher association with CVE. METHODS: Seventy patients (mean LVEF: 25 +/- 11%) considered for revascularization or medical management +/- implantable cardiac defibrillator were enrolled. A 1.5-T GE MRI (Signa, GE Healthcare, Milwaukee, Wisconsin) was used to acquire cine and delayed enhancement images. The patients' core and border zones of infarcted myocardium were analyzed and followed for CVE. RESULTS: Larger infarct border zone and its percentage of myocardium were found in the 29 patients (41%) who had CVE (median 13.3 g [interquartile range (IQR) 8.4 to 25.1 g] vs. 8.0 g [IQR 3.0 to 14.5 g], p = 0.02 and 7.8% [IQR 4.9% to 17.0%] vs. 4.1% [IQR 1.9% to 9.3%], p = 0.02, respectively). The core infarct zone and its percentage of myocardium, left ventricular end-diastolic volume, left ventricular end-systolic volume, and LVEF were not statistically significant. Sub-analysis of the medical management and revascularization patients with CVE demonstrated that the medically managed patients had a larger border zone, whereas there was no difference between border and core zones in the revascularization group (p < 0.05). CONCLUSIONS: Quantification of core and border zones and their percentages of myocardium through CMR is associated with future CVE and might assist in the management of patients with ICM.


Subject(s)
Cardiac Catheterization , Cardiomyopathies/complications , Magnetic Resonance Imaging/methods , Myocardial Infarction/diagnosis , Myocardium/pathology , Cardiomyopathies/diagnosis , Cardiomyopathies/physiopathology , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/physiopathology , Prognosis , Reproducibility of Results , Stroke Volume/physiology , Ventricular Function, Left/physiology
20.
J Cardiovasc Magn Reson ; 12: 75, 2010 Dec 30.
Article in English | MEDLINE | ID: mdl-21192815

ABSTRACT

BACKGROUND: Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort. RESULTS: Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03). CONCLUSIONS: Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.


Subject(s)
Calcinosis/diagnosis , Coronary Artery Disease/diagnosis , Diabetes Mellitus, Type 2/complications , Magnetic Resonance Imaging , Age Factors , Aged , Asymptomatic Diseases , Calcinosis/etiology , Calcinosis/pathology , California , Chi-Square Distribution , Cohort Studies , Coronary Artery Disease/etiology , Coronary Artery Disease/pathology , Diabetes Mellitus, Type 2/pathology , Female , Humans , Linear Models , Male , Middle Aged , Observer Variation , Predictive Value of Tests , Reproducibility of Results , Risk Assessment , Risk Factors
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