Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. METHODS: Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. RESULTS: Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. CONCLUSIONS: Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.

Non-electrocardiogram-gated, free-breathing, off-resonance reduced, high-resolution, whole-heart myocardial T2 * mapping at 3 T within 5 min.

PURPOSE: Widely used conventional 2D T2 * approaches that are based on breath-held, electrocardiogram (ECG)-gated, multi-gradient-echo sequences are prone to motion artifacts in the presence of incomplete breath holding or arrhythmias, which is common in cardiac patients. To address these limitations, a 3D, non-ECG-gated, free-breathing T2 * technique that enables rapid whole-heart coverage was developed and validated. METHODS: A continuous random Gaussian 3D k-space sampling was implemented using a low-rank tensor framework for motion-resolved 3D T2 * imaging. This approach was tested in healthy human volunteers and in swine before and after intravenous administration of ferumoxytol. RESULTS: Spatial-resolution matched T2 * images were acquired with 2-3-fold reduction in scan time using the proposed T2 * mapping approach relative to conventional T2 * mapping. Compared with the conventional approach, T2 * images acquired with the proposed method demonstrated reduced off-resonance and flow artifacts, leading to higher image quality and lower coefficient of variation in T2 *-weighted images of the myocardium of swine and humans. Mean myocardial T2 * values determined using the proposed and conventional approaches were highly correlated and showed minimal bias. CONCLUSION: The proposed non-ECG-gated, free-breathing, 3D T2 * imaging approach can be performed within 5 min or less. It can overcome critical image artifacts from undesirable cardiac and respiratory motion and bulk off-resonance shifts at the heart-lung interface. The proposed approach is expected to facilitate faster and improved cardiac T2 * mapping in those with limited breath-holding capacity or arrhythmias.

Artificial Intelligence for Contrast-Free MRI: Scar Assessment in Myocardial Infarction Using Deep Learning-Based Virtual Native Enhancement.

BACKGROUND: Myocardial scars are assessed noninvasively using cardiovascular magnetic resonance late gadolinium enhancement (LGE) as an imaging gold standard. A contrast-free approach would provide many advantages, including a faster and cheaper scan without contrast-associated problems. METHODS: Virtual native enhancement (VNE) is a novel technology that can produce virtual LGE-like images without the need for contrast. VNE combines cine imaging and native T1 maps to produce LGE-like images using artificial intelligence. VNE was developed for patients with previous myocardial infarction from 4271 data sets (912 patients); each data set comprises slice position-matched cine, T1 maps, and LGE images. After quality control, 3002 data sets (775 patients) were used for development and 291 data sets (68 patients) for testing. The VNE generator was trained using generative adversarial networks, using 2 adversarial discriminators to improve the image quality. The left ventricle was contoured semiautomatically. Myocardial scar volume was quantified using the full width at half maximum method. Scar transmurality was measured using the centerline chord method and visualized on bull's-eye plots. Lesion quantification by VNE and LGE was compared using linear regression, Pearson correlation (R), and intraclass correlation coefficients. Proof-of-principle histopathologic comparison of VNE in a porcine model of myocardial infarction also was performed. RESULTS: VNE provided significantly better image quality than LGE on blinded analysis by 5 independent operators on 291 data sets (all P<0.001). VNE correlated strongly with LGE in quantifying scar size (R, 0.89; intraclass correlation coefficient, 0.94) and transmurality (R, 0.84; intraclass correlation coefficient, 0.90) in 66 patients (277 test data sets). Two cardiovascular magnetic resonance experts reviewed all test image slices and reported an overall accuracy of 84% for VNE in detecting scars when compared with LGE, with specificity of 100% and sensitivity of 77%. VNE also showed excellent visuospatial agreement with histopathology in 2 cases of a porcine model of myocardial infarction. CONCLUSIONS: VNE demonstrated high agreement with LGE cardiovascular magnetic resonance for myocardial scar assessment in patients with previous myocardial infarction in visuospatial distribution and lesion quantification with superior image quality. VNE is a potentially transformative artificial intelligence-based technology with promise in reducing scan times and costs, increasing clinical throughput, and improving the accessibility of cardiovascular magnetic resonance in the near future.

Perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: Preliminary data.

PURPOSE: To demonstrate the feasibility of mapping cerebral perfusion metrics with BOLD MRI during modulation of pulmonary venous oxygen saturation. METHODS: A gas blender with a sequential gas delivery breathing circuit was used to implement rapid isocapnic changes in the partial pressure of oxygen of the arterial blood. Partial pressure of oxygen was initially lowered to a baseline of 40 mmHg. It was then rapidly raised to 95 mmHg for 20 s before rapidly returning to baseline. The induced cerebral changes in deoxyhemoglobin concentration were tracked over time using BOLD MRI in 6 healthy subjects and 1 patient with cerebral steno-occlusive disease. BOLD signal change, contrast-to-noise ratio, and time delay metrics were calculated. Perfusion metrics such as mean transit time, relative cerebral blood volume, and relative cerebral blood flow were calculated using a parametrized method with a mono-exponential residue function. An arterial input function from within the middle cerebral artery was used to scale relative cerebral blood volume and calculate absolute cerebral blood volume and cerebral blood flow. RESULTS: In normal subjects, average gray and white matter were: BOLD change = 6.3 ± 1.2% and 2.5 ± 0.6%, contrast-to-noise ratio = 4.3 ± 1.3 and 2.6 ± 0.7, time delay = 2.3 ± 0.6 s and 3.6 ± 0.7 s, mean transit time = 3.9 ± 0.6 s and 5.5 ± 0.6 s, relative cerebral blood volume = 3.7 ± 0.9 and 1.6 ± 0.4, relative cerebral blood flow = 70.1 ± 8.3 and 20.6 ± 4.0, cerebral blood flow volume = 4.1 ± 0.9 mL/100 g and 1.8 ± 0.5 mL/100 g, and cerebral blood flow = 97.2 ± 18.7 mL/100 g/min and 28.7 ± 5.9 mL/100 g/min. CONCLUSION: This study demonstrates that induced abrupt changes in deoxyhemoglobin can function as a noninvasive vascular contrast agent that may be used for cerebral perfusion imaging.

Quantification of myocardial hemorrhage using T2* cardiovascular magnetic resonance at 1.5T with ex-vivo validation.

BACKGROUND: T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information. METHODS: ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*. RESULTS: While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*. CONCLUSION: Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.

Retrospective assessment of at-risk myocardium in reperfused acute myocardial infarction patients using contrast-enhanced balanced steady-state free-precession cardiovascular magnetic resonance at 3T with SPECT validation.

BACKGROUND: Contrast-enhanced (CE) steady-state free precession (SSFP) CMR at 1.5T has been shown to be a valuable alternative to T2-based methods for the detection and quantifications of area-at-risk (AAR) in acute myocardial infarction (AMI) patients. However, CE-SSFP's capacity for assessment of AAR at 3T has not been investigated. We examined the clinical utility of CE-SSFP and T2-STIR for the retrospective assessment of AAR at 3T with single-photon-emission-computed tomography (SPECT) validation. MATERIALS AND METHODS: A total of 60 AMI patients (ST-elevation AMI, n = 44;  non-ST-elevation AMI, n = 16) were recruited into the CMR study between 3 and 7 days post revascularization. All patients underwent T2-STIR, CE-bSSFP and late-gadolinium-enhancement CMR. For validation, SPECT images were acquired in a subgroup of patients (n = 30). RESULTS: In 53 of 60 patients (88 %), T2-STIR was of diagnostic quality compared with 54 of 60 (90 %) with CE-SSFP. In a head-to-head per-slice comparison (n = 365), there was no difference in AAR quantified using T2-STIR and CE-SSFP (R2 = 0.92, p < 0.001; bias:-0.4 ± 0.8 cm2, p = 0.46). On a per-patient basis, there was good agreement between CE-SSFP (n = 29) and SPECT (R2 = 0.86, p < 0.001; bias: - 1.3 ± 7.8 %LV, p = 0.39) for AAR determination. T2-STIR also showed good agreement with SPECT for AAR measurement (R2 = 0.81, p < 0.001, bias: 0.5 ± 11.1 %LV, p = 0.81). There was also a strong agreement between CE-SSFP and T2-STIR with respect to the assessment of AAR on per-patient analysis (R2 = 0.84, p < 0.001, bias: - 2.1 ± 10.1 %LV, p = 0.31). CONCLUSIONS: At 3T, both CE-SSFP and T2-STIR can retrospectively quantify the at-risk myocardium with high accuracy.

Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance.

BACKGROUND: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. MATERIALS AND METHODS: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. RESULTS: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths. CONCLUSION: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.

Heart Rate-Independent 3D Myocardial Blood Oxygen Level-Dependent MRI at 3.0 T with Simultaneous 13N-Ammonia PET Validation.

Background Despite advances, blood oxygen level-dependent (BOLD) cardiac MRI for myocardial perfusion is limited by inadequate spatial coverage, imaging speed, multiple breath holds, and imaging artifacts, particularly at 3.0 T. Purpose To develop and validate a robust, contrast agent-unenhanced, free-breathing three-dimensional (3D) cardiac MRI approach for reliably examining changes in myocardial perfusion between rest and adenosine stress. Materials and Methods A heart rate-independent, free-breathing 3D T2 mapping technique at 3.0 T that can be completed within the period of adenosine stress (≤4 minutes) was developed by using computer simulations, ex vivo heart preparations, and dogs. Studies in dogs were performed with and without coronary stenosis and validated with simultaneously acquired nitrogen 13 (13N) ammonia PET perfusion in a clinical PET/MRI system. The MRI approach was also prospectively evaluated in healthy human volunteers (from January 2017 to September 2017). Myocardial BOLD responses (MBRs) between normal and ischemic myocardium were compared with mixed model analysis. Results Dogs (n = 10; weight range, 20-25 kg; mongrel dogs) and healthy human volunteers (n = 10; age range, 22-53 years; seven men) were evaluated. In healthy dogs, T2 MRI at adenosine stress was greater than at rest (mean rest vs stress, 38.7 msec ± 2.5 [standard deviation] vs 45.4 msec ± 3.3, respectively; MBR, 1.19 ± 0.08; both, P < .001). At the same conditions, mean rest versus stress PET perfusion was 1.1 mL/mg/min ± 0.11 versus 2.3 mL/mg/min ± 0.82, respectively (P < .001); myocardial perfusion reserve (MPR) was 2.4 ± 0.82 (P < .001). The BOLD response and PET MPR were positively correlated (R = 0.67; P < .001). In dogs with coronary stenosis, perfusion anomalies were detected on the basis of MBR (normal vs ischemic, 1.09 ± 0.05 vs 1.00 ± 0.04, respectively; P < .001) and MPR (normal vs ischemic, 2.7 ± 0.08 vs 1.7 ± 1.1, respectively; P < .001). Human volunteers showed increased myocardial T2 at stress (rest vs stress, 44.5 msec ± 2.6 vs 49.0 msec ± 5.5, respectively; P = .004; MBR, 1.1 msec ± 8.08). Conclusion This three-dimensional cardiac blood oxygen level-dependent (BOLD) MRI approach overcame key limitations associated with conventional cardiac BOLD MRI by enabling whole-heart coverage within the standard duration of adenosine infusion, and increased the magnitude and reliability of BOLD contrast, which may be performed without requiring breath holds. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

Cardiovascular Magnetic Resonance in Acute ST-Segment-Elevation Myocardial Infarction: Recent Advances, Controversies, and Future Directions.

Although mortality after ST-segment elevation myocardial infarction (MI) is on the decline, the number of patients developing heart failure as a result of MI is on the rise. Apart from timely reperfusion by primary percutaneous coronary intervention, there is currently no established therapy for reducing MI size. Thus, new cardioprotective therapies are required to improve clinical outcomes after ST-segment-elevation MI. Cardiovascular magnetic resonance has emerged as an important imaging modality for assessing the efficacy of novel therapies for reducing MI size and preventing subsequent adverse left ventricular remodeling. The recent availability of multiparametric mapping cardiovascular magnetic resonance imaging has provided new insights into the pathophysiology underlying myocardial edema, microvascular obstruction, intramyocardial hemorrhage, and changes in the remote myocardial interstitial space after ST-segment-elevation MI. In this article, we provide an overview of the recent advances in cardiovascular magnetic resonance imaging in reperfused patients with ST-segment-elevation MI, discuss the controversies surrounding its use, and explore future applications of cardiovascular magnetic resonance in this setting.

First-pass myocardial perfusion MRI with reduced subendocardial dark-rim artifact using optimized Cartesian sampling.

PURPOSE: The presence of subendocardial dark-rim artifact (DRA) remains an ongoing challenge in first-pass perfusion (FPP) cardiac magnetic resonance imaging (MRI). We propose a free-breathing FPP imaging scheme with Cartesian sampling that is optimized to minimize the DRA and readily enables near-instantaneous image reconstruction. MATERIALS AND METHODS: The proposed FPP method suppresses Gibbs ringing effects-a major underlying factor for the DRA-by "shaping" the underlying point spread function through a two-step process: 1) an undersampled Cartesian sampling scheme that widens the k-space coverage compared to the conventional scheme; and 2) a modified parallel-imaging scheme that incorporates optimized apodization (k-space data filtering) to suppress Gibbs-ringing effects. Healthy volunteer studies (n = 10) were performed to compare the proposed method against the conventional Cartesian technique-both using a saturation-recovery gradient-echo sequence at 3T. Furthermore, FPP imaging studies using the proposed method were performed in infarcted canines (n = 3), and in two symptomatic patients with suspected coronary microvascular dysfunction for assessment of myocardial hypoperfusion. RESULTS: Width of the DRA and the number of DRA-affected myocardial segments were significantly reduced in the proposed method compared to the conventional approach (width: 1.3 vs. 2.9 mm, P < 0.001; number of segments: 2.6 vs. 8.7; P < 0.0001). The number of slices with severe DRA was markedly lower for the proposed method (by 10-fold). The reader-assigned image quality scores were similar (P = 0.2), although the quantified myocardial signal-to-noise ratio was lower for the proposed method (P < 0.05). Animal studies showed that the proposed method can detect subendocardial perfusion defects and patient results were consistent with the gold-standard invasive test. CONCLUSION: The proposed free-breathing Cartesian FPP imaging method significantly reduces the prevalence of severe DRAs compared to the conventional approach while maintaining similar resolution and image quality. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:542-555.

Free-breathing, motion-corrected, highly efficient whole heart T2 mapping at 3T with hybrid radial-cartesian trajectory.

PURPOSE: To develop and test a time-efficient, free-breathing, whole heart T2 mapping technique at 3.0T. METHODS: ECG-triggered three-dimensional (3D) images were acquired with different T2 preparations at 3.0T during free breathing. Respiratory motion was corrected with a navigator-guided motion correction framework at near perfect efficiency. Image intensities were fit to a monoexponential function to derive myocardial T2 maps. The proposed 3D, free breathing, motion-corrected (3D-FB-MoCo) approach was studied in ex vivo canine hearts and kidneys, healthy volunteers, and canine subjects with acute myocardial infarction (AMI). RESULTS: Ex vivo T2 values from proposed 3D T2 -prep gradient echo were not different from two-dimensional (2D) spin echo (P = 0.7) and T2 -prep balanced steady-state free precession (bSSFP) (P = 0.7). In healthy volunteers, compared with 3D-FB-MoCo and breath-held 2D T2 -prep bSSFP (2D-BH), non-motion-corrected (3D-FB-Non-MoCo) myocardial T2 was longer, had a larger coefficient of variation (COV), and had a lower image quality (IQ) score (T2 = 40.3 ms, COV = 38%, and IQ = 2.3; all P < 0.05). Conversely, the mean and COV and IQ of 3D-FB-MoCo (T2 = 37.7 ms, COV = 17%, and IQ = 3.5) and 2D-BH (T2 = 38.0 ms, COV = 15%, and IQ = 3.8) were not different (P = 0.99, P = 0.74, and P = 0.14, respectively). In AMI, T2 values and edema volumes from 3D-FB-MoCo and 2D-BH were closely correlated (R(2) = 0.88 and 0.96, respectively). CONCLUSION: The proposed whole heart T2 mapping approach can be performed within 5 min with similar accuracy to that of the 2D-BH T2 mapping approach.

All-systolic non-ECG-gated myocardial perfusion MRI: Feasibility of multi-slice continuous first-pass imaging.

PURPOSE: To develop and test the feasibility of a new method for non-ECG-gated first-pass perfusion (FPP) cardiac MR capable of imaging multiple short-axis slices at the same systolic cardiac phase. METHODS: A magnetization-driven pulse sequence was developed for non-ECG-gated FPP imaging without saturation-recovery preparation using continuous slice-interleaved radial sampling. The image reconstruction method, dubbed TRACE, used self-gating based on reconstruction of a real-time image-based navigator combined with reference-constrained compressed sensing. Data from ischemic animal studies (n = 5) was used in a simulation framework to evaluate temporal fidelity. Healthy subjects (n = 5) were studied using both the proposed approach and the conventional method to compare the myocardial contrast-to-noise ratio (CNR). Patients (n = 2) underwent adenosine stress studies using the proposed method. RESULTS: Temporal fidelity of the developed method was shown to be sufficient at high heart-rates. The healthy volunteers studies demonstrated normal perfusion and no dark-rim artifacts. Compared with the conventional scheme, myocardial CNR for the proposed method was slightly higher (8.6 ± 0.6 versus 8.0 ± 0.7). Patient studies showed stress-induced perfusion defects consistent with invasive angiography. CONCLUSION: The presented methods and results demonstrate feasibility of the proposed approach for high-resolution non-ECG-gated FPP imaging of 3 myocardial slices at the same systolic phase, and indicate its potential for achieving desirable image quality (high CNR and no dark-rim artifacts).

Quantification of myocardial blood flow using non-ECG-triggered MR imaging.

PURPOSE: MR myocardial perfusion imaging is dependent on reliable electrocardiogram (ECG) triggering for accurate measurement of myocardial blood flow (MBF). A non-ECG-triggered method for quantitative first-pass imaging may improve clinical feasibility in patients with poor ECG signal. The purpose of this study is to evaluate the feasibility of a non-ECG-triggered method for myocardial perfusion imaging in a single slice. METHODS: The proposed non-ECG-triggered technique uses a saturation-recovery magnetization preparation and golden-angle radial acquisition for integrated arterial input function (AIF) measurement. Image based self-gating with a temporal resolution of 42.6 ms is used to generate a first-pass image series with consistent cardiac phase. The AIF is measured using beat-by-beat T1 estimation of the ventricular blood pool. The proposed technique was performed on 14 healthy volunteers and compared against a conventional ECG-triggered dual-bolus acquisition. RESULTS: The proposed method produced MBF with no significant difference compared with ECG-triggered technique (mean of 0.63 ± 0.22 mL/min/g to 0.73 ± 0.21 mL/min/g). CONCLUSION: We have developed a non-ECG-triggered perfusion imaging method with T1 based measurement of the AIF in a single slice. In this preliminary study, our results demonstrate that MBF measured using the proposed method is comparable to the conventional ECG-triggered method.

Increased pericardial fat accumulation is associated with increased intramyocardial lipid content and duration of highly active antiretroviral therapy exposure in patients infected with human immunodeficiency virus: a 3T cardiovascular magnetic resonance feasibility study.

BACKGROUND: The aim of the current study was to examine whether the use of highly active antiretroviral therapy (HAART) in patients with HIV is associated with changes in pericardial fat and myocardial lipid content measured by cardiovascular magnetic resonance (CMR). METHODS: In this prospective case-control study, we compared 27 HIV seropositive (+) male subjects receiving HAART to 22 control male subjects without HIV matched for age, ethnicity and body mass index. All participants underwent CMR imaging for determination of pericardial fat [as volume at the level of the origin of the left main coronary artery (LM) and at the right ventricular free wall] and magnetic resonance spectroscopy (MRS) for evaluation of intramyocardial lipid content (% of fat to water in a single voxel at the interventricular septum). All measurements were made by two experienced readers blinded to the clinical history of the study participants. Two-sample t-test, Spearman's correlation coefficient or Pearson's correlation coefficient and multivariable logistic regression were used for statistical analysis. RESULTS: Pericardial fat volume at the level of LM origin was higher in HIV (+) subjects (33.4 cm(3) vs. 27.4 cm(3), p = 0.03). On multivariable analysis adjusted for age, Framingham risk score (FRS) and waist/hip ratio, pericardial fat remained significantly associated to HIV-status (OR 1.09, p = 0.047). For both HIV (+) and HIV (-) subjects, pericardial fat volume showed strong correlation with intramyocardial lipid content (r = 0.58, p < 0.0001) and FRS (r = 0.53, p = 0.0002). Among HIV (+) subjects, pericardial fat was significantly higher in patients with lipo-accumulation (37 cm(3) vs. 27.1 cm(3), p = 0.03) and showed significant correlation with duration of both HIV infection (r = 0.5, p = 0.01) and HAART (r = 0.46, p = 0.02). CONCLUSIONS: Pericardial fat content is increased in HIV (+) subjects on chronic HAART (>5 years), who demonstrate HAART-related lipo-accumulation and prolonged HIV duration of infection. Further investigation is warranted to determine whether increased pericardial fat is associated with higher cardiovascular risk leading to premature cardiovascular events in this patient population.

Correlation of scar in cardiac MRI and high-resolution contact mapping of left ventricle in a chronic infarct model.

BACKGROUND: Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra-high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model. METHODS: Chronic infarcts were created in five anesthetized dogs by ligating the left anterior descending coronary artery. Late gadolinium-enhanced magnetic resonance imaging (LGE MRI) was obtained 4.9 ± 0.9 months after infarction, with three-dimensional (3D) gadolinium enhancement signal intensity maps at 1-mm and 5-mm depths from the endocardium. Ultra-high resolution electroanatomical maps were created using a novel mapping system (Rhythmia Mapping System, Rhythmia Medical/Boston Scientific, Marlborough, MA, USA) Rhythmia Medical, Boston Scientific, Marlborough, MA, USA with an 8.5F catheter with mini-basket electrode array (64 tiny electrodes, 2.5-mm spacing, center-to-center). RESULTS: The maps contained 7,754 ± 1,960 electrograms per animal with a mean resolution of 2.8 ± 0.6 mm. Low bipolar voltage (<2 mV) correlated closely with scar on the LGE MRI and the 3D signal intensity map (1-mm depth). The scar areas between the MRI signal intensity map and electroanatomic map matched at 87.7% of sites. Bipolar and unipolar voltages, compared in 592 electrograms from four MRI-defined scar types (endocardial scar, epicardial scar, mottled transmural scar, and dense transmural scar) as well as normal tissue, were significantly different. A unipolar voltage of <13 mV correlated with transmural extension of scar in MRI. Electrograms exhibiting isolated late potentials (ILPs) were manually annotated and ILP maps were created showing ILP location and timing. ILPs were identified in 203 ± 159 electrograms per dog (within low-voltage areas) and ILP maps showed gradation in timing of ILPs at different locations in the scar. CONCLUSIONS: Ultra-high resolution contact electroanatomical mapping accurately localizes ventricular scar and abnormal myocardial tissue in this chronic canine infarct model. The high fidelity electrograms provided clear identification of the very low amplitude ILPs within the scar tissue and has the potential to quickly identify targets for ablation.

Validation of contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model of convalescent myocardial infarction.

BACKGROUND: Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium after myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. METHODS AND RESULTS: Yucatan minipigs underwent induction of MI and 2-3 weeks later were randomized to receive intracoronary infusion of 12.5×10(6) mismatched allogeneic CDCs or vehicle. Allogeneic CDCs induced mild local mononuclear infiltration but no systemic immunogenicity. MRI revealed that allogeneic CDCs attenuated remodeling, improved global and regional function, decreased scar size, and increased viable myocardium compared with placebo 2 months post-treatment. Extensive histological analysis validated quantitatively the MRI measurements of scar size, scar mass, and viable mass. CDCs neither altered gadolinium contrast myocardial kinetics nor induced changes in vascular density or architecture in viable and scarred myocardium. Histology demonstrated that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis). CONCLUSIONS: Contrast-enhanced MRI accurately measures scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. MRI represents a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy.