Association of increased epicardial adipose tissue derived from cardiac magnetic resonance imaging with myocardial fibrosis in Duchenne muscular dystrophy: a clinical prediction model development and validation study in 283 participants.

Background: Epicardial adipose tissue (EAT) contributes to inflammation and fibrosis of the neighboring myocardial tissue via paracrine signaling. In this retrospective study, we investigated the abnormal changes in the amount of EAT in male children with Duchenne muscular dystrophy (DMD) using cardiac magnetic resonance (CMR) imaging. Furthermore, we constructed and validated a nomogram including EAT-related CMR imaging parameter for predicting the occurrence of myocardial fibrosis in patients with DMD. Methods: This study enrolled 283 patients with DMD and 57 healthy participants who underwent CMR acquisitions to measure the quantitative parameters of EAT, pericardial adipose tissue (PAT), paracardial adipose tissue, and subcutaneous adipose tissue. Late gadolinium enhancement (LGE) was performed to confirm myocardial fibrosis in patients with DMD. The DMD group consisted of 200 patients from institution 1 (the ratio of the training set and the internal validation set was 7:3) and 83 patients from four other institutions (the external validation set). Logistic and least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal predictors and to develop and validate the nomogram model predicting LGE risk in the training set, internal validation set, and external validation set. Results: Compared with those in healthy controls, some regional EAT thicknesses, areas, and global volumes were significantly higher in patients with DMD, and 41.7% of patients with DMD showed positive LGE. These LGE-positive patients with DMD showed significantly higher EAT volume (median 23.9 mL/m3; P<0.001) and PAT volume (median 31.8 mL/m3; P<0.001) compared with the LGE-negative patients with DMD. Age [odds ratio (OR) 2.0; P<0.001], body fat percentage (OR 1.3; P<0.001), and EAT volume (OR 1.4; P<0.001) were independently associated with positive LGE in the training set. The interactive dynamic nomogram showed superior prediction performance, with a high degree of the calibration, discrimination, and clinical net benefit in the training and validation of the DMD datasets. The area under the curve (AUC) values of the nomogram in the training set, internal validation set, and external validation set were 0.95 [95% confidence interval (CI): 0.91-0.98], 0.97 (95% CI: 0.92-0.99), and 0.95 (95% CI: 0.91-0.99), respectively. Conclusions: The onset of LGE-based myocardial fibrosis was associated with EAT volume in patients with DMD. Additionally, the nomogram with EAT volumes showed superior performance in patients with DMD for predicting the occurrence of myocardial fibrosis.

Accelerated cardiac T1 mapping in four heartbeats with inline MyoMapNet: a deep learning-based T1 estimation approach.

PURPOSE: To develop and evaluate MyoMapNet, a rapid myocardial T1 mapping approach that uses fully connected neural networks (FCNN) to estimate T1 values from four T1-weighted images collected after a single inversion pulse in four heartbeats (Look-Locker, LL4). METHOD: We implemented an FCNN for MyoMapNet to estimate T1 values from a reduced number of T1-weighted images and corresponding inversion-recovery times. We studied MyoMapNet performance when trained using native, post-contrast T1, or a combination of both. We also explored the effects of number of T1-weighted images (four and five) for native T1. After rigorous training using in-vivo modified Look-Locker inversion recovery (MOLLI) T1 mapping data of 607 patients, MyoMapNet performance was evaluated using MOLLI T1 data from 61 patients by discarding the additional T1-weighted images. Subsequently, we implemented a prototype MyoMapNet and LL4 on a 3 T scanner. LL4 was used to collect T1 mapping data in 27 subjects with inline T1 map reconstruction by MyoMapNet. The resulting T1 values were compared to MOLLI. RESULTS: MyoMapNet trained using a combination of native and post-contrast T1-weighted images had excellent native and post-contrast T1 accuracy compared to MOLLI. The FCNN model using four T1-weighted images yields similar performance compared to five T1-weighted images, suggesting that four T1 weighted images may be sufficient. The inline implementation of LL4 and MyoMapNet enables successful acquisition and reconstruction of T1 maps on the scanner. Native and post-contrast myocardium T1 by MOLLI and MyoMapNet was 1170 ± 55 ms vs. 1183 ± 57 ms (P = 0.03), and 645 ± 26 ms vs. 630 ± 30 ms (P = 0.60), and native and post-contrast blood T1 was 1820 ± 29 ms vs. 1854 ± 34 ms (P = 0.14), and 508 ± 9 ms vs. 514 ± 15 ms (P = 0.02), respectively. CONCLUSION: A FCNN, trained using MOLLI data, can estimate T1 values from only four T1-weighted images. MyoMapNet enables myocardial T1 mapping in four heartbeats with similar accuracy as MOLLI with inline map reconstruction.

Time-efficient and contrast-free magnetic resonance imaging approach to the diagnosis of deep vein thrombosis on black-blood gradient-echo sequence: a pilot study.

BACKGROUND: Black-blood thrombus imaging (BTI) has shown to be advantageous for the diagnosis of deep vein thrombosis (DVT). However, previous techniques using fast spin echo have a high specific absorption rate. As DANTE (delay alternating with nutation for tailored excitation) black-blood preparation can suppress blood flows over a broad range of velocities, we hypothesized that a DANTE black-blood preparation combined with a fast low-angle shot (FLASH) gradient-echo readout-DANTE-FLASH could be used to diagnose DVT. METHODS: Eleven healthy volunteers and 30 suspected DVT patients were recruited to undergo DANTE-FLASH and magnetic resonance direct thrombus imaging (MRDTI). The suspected DVT patients were also examined by ultrasound (US). For the segment level, a total of 1,066 venous vessel segments were analyzed. Using US and MRDTI as the references, the sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV), and accuracy (ACC) of DANTE-FLASH were calculated. To quantitatively compare image quality between DANTE-FLASH and MRDTI, image signal-to-noise ratio (SNR), apparent contrast-to-noise ratio (CNR) between muscle and the venous lumen, and the apparent CNR between the thrombus and venous lumen were measured. Additionally, diagnostic confidence, image quality, and clot burden were also evaluated. RESULTS: Using the consensus results of US and MRDTI as a standard reference, the diagnostic SE, SP, PPV, NPV, and ACC of DANTE-FLASH for the 2 readers were 97.0% and 93.2%, 99.0% and 98.2%, 93.4% and 87.9%, 99.6% and 99.0%, and 98.8% and 97.6%, respectively. According to the image quantitative analysis results, DANTE-FLASH demonstrated higher image SNR and CNR than MRDTI. The image quality and diagnostic confidence scores of DANTE-FLASH were higher than MRDTI (3.66±0.44 vs. 3.52±0.52, P<0.001, and 3.84±0.36 vs. 3.76±0.41, P<0.001). There was excellent agreement between DANTE-FLASH and MRDTI on clot burden evaluation. CONCLUSIONS: DANTE-FLASH provided better image quality than MRDTI and accurately detected thrombi. It may, therefore, serve as a safe and convenient alternative for the diagnosis of DVT.

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.

A post-processing method based on interphase motion correction and averaging to improve image quality of 4D magnetic resonance imaging: a clinical feasibility study.

METHODS:: Nine patients (seven pancreas, one liver, and one lung) were recruited. 4D-MRI was performed using two prototype k-space sorted techniques, stack-of-stars (SOS) and koosh-ball (KB) acquisitions. Post-processing using MoCoAve was implemented for both methods. Image quality score, apparent SNR (aSNR), sharpness, motion trajectory and standard deviation (σ_GTV) of the gross tumor volumes were compared between original and MoCoAve image sets. RESULTS:: All subjects successfully underwent 4D-MRI scans and MoCoAve was performed on all data sets. Significantly higher image quality scores (2.64 ± 0.39 vs 1.18 ± 0.34, p = 0.001) and aSNR (37.6 ± 15.3 vs 18.1 ± 5.7, p = 0.001) was observed in the MoCoAve images when compared to the original images. High correlation in tumor motion trajectories in the superoinferior direction (SI: 0.91 ± 0.08) and weaker in the anteroposterior (AP: 0.51 ± 0.44) and mediolateral (ML: 0.37 ± 0.23) directions, similar image sharpness (0.367 ± 0.068 vs 0.369 ± 0.072, p = 0.805), and minimal average absolute difference (0.47 ± 0.34 mm) of the motion trajectory profiles was found between the two image sets. The σ_GTV in pancreas patients was significantly (p = 0.039) lower in MoCoAve images (1.48 ± 1.35 cm3) than in the original images (2.17 ± 1.31 cm3). CONCLUSION:: MoCoAve using interphase motion correction and averaging has shown promise as a post-processing method for improving k-space sorted (SOS and KB) 4D-MRI image quality in thoracic and abdominal cancer patients. ADVANCES IN KNOWLEDGE:: The proposed method is an image based post-processing method that could be applied to many k-space sorted 4D-MRI methods for improved image quality and signal-to-noise ratio while preserving image sharpness and respiratory motion fidelity. It is a useful technique for the radiotherapy planning community who are interested in using 4D-MRI but aren't satisfied with their current MR image quality.

Novel 4D-MRI of tumor infiltrating vasculature: characterizing tumor and vessel volume motion for selective boost volume definition in pancreatic radiotherapy.

BACKGROUND: Pancreatic ductal adenocarcinoma has dismal prognosis. Most patients receive radiation therapy (RT), which is complicated by respiration induced organ motion in upper abdomen. The purpose of this study is to report our early clinical experience in a novel self-gated k-space sorted four-dimensional magnetic resonance imaging (4D-MRI) with slab-selective (SS) excitation to highlight tumor infiltrating blood vessels for pancreatic RT. METHODS: Ten consecutive patients with borderline resectable or locally advanced pancreatic cancer were recruited to the study. Non-contrast 4D-MRI with and without slab-selective excitation and 4D-CT with delay contrast were performed on all patients. Vessel-tissue CNR were calculated for aorta and critical vessels (superior mesenteric artery or superior mesenteric vein) encompassed by tumor. Respiratory motion trajectories for tumor, as well as involved vessels were analyzed on SS-4D-MRI. Intra-class cross correlation (ICC) between tumor volume and involved vessels were calculated. RESULTS: Among all 4D imaging modalities evaluated, SS-4D-MRI sampling trajectory results in images with highest vessel-tissue CNR comparing to non-slab-selective 4D-MRI and 4D-CT for all patients studied. Average (±standard deviation) CNR for involved vessels are 13.1 ± 8.4 and 3.2 ± 2.7 for SS-4D-MRI and 4D-CT, respectively. The ICC factors comparing tumor and involved vessels motion trajectories are 0.93 ± 0.10, 0.65 ± 0.31 and 0.77 ± 0.23 for superior-inferior, anterior-posterior and medial-lateral directions respectively. CONCLUSIONS: A novel 4D-MRI sequence based on 3D-radial sampling and slab-selective excitation has been assessed for pancreatic cancer patients. The non-contrast 4D-MRI images showed significantly better contrast to noise ratio for the vessels that limit tumor resectability compared to 4D-CT with delayed contrast. The sequence has great potential in accurately defining both the tumor and boost volume margins for pancreas RT with simultaneous integrated boost.

Atherosclerosis T1-weighted characterization (CATCH): evaluation of the accuracy for identifying intraplaque hemorrhage with histological validation in carotid and coronary artery specimens.

BACKGROUND: Coronary high intensity plaques (CHIPs) detected using cardiovascular magnetic resonance (CMR) coronary atherosclerosis T1-weighted characterization with integrated anatomical reference (CATCH) have been shown to be positively associated with high-risk morphology observed on intracoronary optical coherence tomography (OCT). This study sought to validate whether CHIPs detected on CATCH indicate the presence of intraplaque hemorrhage (IPH) through ex vivo imaging of carotid and coronary plaque specimens, with histopathology as the standard reference. METHODS: Ten patients scheduled to undergo carotid endarterectomy underwent CMR with the conventional T1-weighted (T1w) sequence. Eleven carotid atherosclerotic plaques removed at carotid endarterectomy and six coronary artery endarterectomy specimens removed from patients undergoing coronary artery bypass grafting (CABG) were scanned ex vivo using both the conventional T1w sequence and CATCH. Both in vivo and ex vivo images were examined for the presence of IPH. The sensitivity, specificity, and Cohen Kappa (k) value of each scan were calculated using matched histological sections as the reference. k value between each scan in the discrimination of IPH was also computed. RESULTS: A total of 236 in vivo locations, 328 ex vivo and matching histology locations were included for the analysis. Sensitivity, specificity, and k value were 76.7%, 95.3%, and 0.75 for in vivo T1w imaging, 77.2%, 97.4%, and 0.78 for ex vivo T1w imaging, and 95.0%, 92.1%, and 0.84 for ex vivo CATCH, respectively. Moderate agreement was reached between in vivo T1w imaging, ex vivo T1w imaging, and ex vivo CATCH for the detection of IPH: between in vivo T1w imaging and ex vivo CATCH (k = 0.68), between ex vivo T1w imaging and ex vivo CATCH (k = 0.74), between in vivo T1w imaging and ex vivo T1w imaging (k = 0.83). None of the coronary artery plaque locations showed IPH. CONCLUSION: This study demonstrated that carotid CHIPs detected by CATCH can be used to assess for IPH, a high-risk plaque feature.

Diffusion Tensor Cardiac Magnetic Resonance Reveals Exosomes From Cardiosphere-Derived Cells Preserve Myocardial Fiber Architecture After Myocardial Infarction.

The object of the study was to reveal the fiber microstructural response with diffusion tensor cardiac magnetic resonance after intramyocardial exosomes secreted by cardiosphere-derived cells (CDCEXO) in chronic porcine myocardial infarction. Porcine with myocardial infarction underwent intramyocardial delivery of human CDCEXO and placebo in a randomized placebo-controlled study. Four weeks after injection, viability improved in the CDCEXO group, whereas myocardial fiber architecture and cardiac function were preserved. In the placebo group, fiber architecture and cardiac function declined. Myocardial regeneration by CDCEXO is not tumor-like; instead, details of tissue architecture are faithfully preserved, which may foster physiological excitation and contraction.

Improved vessel-tissue contrast and image quality in 3D radial sampling-based 4D-MRI.

PURPOSE: In radiation treatment planning for thoracic and abdominal tumors, 4D-MRI has shown promise in respiratory motion characterization with improved soft-tissue contrast compared to clinical standard, 4D computed tomography (4D-CT). This study aimed to further improve vessel-tissue contrast and overall image quality in 3D radial sampling-based 4D-MRI using a slab-selective (SS) excitation approach. METHODS: The technique was implemented in a 3D radial sampling with self-gating-based k-space sorting sequence. The SS excitation approach was compared to a non-selective (NS) approach in six cancer patients and two healthy volunteers at 3T. Improvements in vessel-tissue contrast ratio (CR) and vessel signal-to-noise ratio (SNR) were analyzed in five of the eight subjects. Image quality was visually assessed in all subjects on a 4-point scale (0: poor; 3: excellent). Tumor (patients) and pancreas (healthy) motion trajectories were compared between the two imaging approaches. RESULTS: Compared with NS-4D-MRI, SS-4D-MRI significantly improved the overall vessel-tissue CR (2.60 ± 3.97 vs. 1.03 ± 1.44, P < 0.05), SNR (63.33 ± 38.45 vs. 35.74 ± 28.59, P < 0.05), and image quality score (2.6 ± 0.5 vs. 1.4 ± 0.5, P = 0.02). Motion trajectories from the two approaches exhibited strong correlation in the superior-inferior (0.96 ± 0.06), but weaker in the anterior-posterior (0.78 ± 0.24) and medial-lateral directions (0.46 ± 0.44). CONCLUSIONS: The proposed 4D-MRI with slab-selectively excited 3D radial sampling allows for improved blood SNR, vessel-tissue CR, and image quality.

Incremental Value of Plaque Enhancement in Patients with Moderate or Severe Basilar Artery Stenosis: 3.0 T High-Resolution Magnetic Resonance Study.

AIM: To investigate the clinical relevance of plaque's morphological characteristics and distribution pattern using 3.0 T high-resolution magnetic resonance imaging (HRMRI) in patients with moderate or severe basilar artery (BA) atherosclerosis stenosis. MATERIALS AND METHODS: Fifty-seven patients (33 symptomatic patients and 24 asymptomatic patients) were recruited for 3.0 T HRMRI scan; all of them had >50% stenosis on the BA. The intraplaque hemorrhage (IPH), contrast-enhancement pattern, and distribution of BA plaques were compared between the symptomatic and asymptomatic groups. Factors potentially associated with posterior ischemic stroke were calculated by multivariate analyses. RESULTS: Enhancement of BA plaque was more frequently observed in symptomatic than in asymptomatic patients (27/33, 81.8% versus 11/24, 45.8%; p < 0.01). In multivariate regression analysis, plaque enhancement (OR = 7.193; 95% CI: 1.880-27.517; p = 0.004) and smoking (OR = 4.402; 95% CI: 2.218-15.909; p = 0.024) were found to be independent risk factors of posterior ischemic events in patients with BA stenosis >50%. Plaques were mainly distributed at the ventral site (39.3%) or involved more than two arcs (21.2%) in the symptomatic group but were mainly distributed at left (33.3%) and right (25.0%) sites in the asymptomatic group.

Arterial CO2 as a Potent Coronary Vasodilator: A Preclinical PET/MR Validation Study with Implications for Cardiac Stress Testing.

Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO2 (PaCO2), particularly with respect to adenosine, is not well characterized because of challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. Methods: By prospectively and independently controlling PaCO2 and combining it with 13N-ammonia PET measurements, we investigated whether a physiologically tolerable hypercapnic stimulus (∼25 mm Hg increase in PaCO2) can increase MBF to that observed with adenosine in 3 groups of canines: without coronary stenosis, subjected to non-flow-limiting coronary stenosis, and after preadministration of caffeine. The extent of effect on MBF due to hypercapnia was compared with adenosine. Results: In the absence of stenosis, mean MBF under hypercapnia was 2.1 ± 0.9 mL/min/g and adenosine was 2.2 ± 1.1 mL/min/g; these were significantly higher than at rest (0.9 ± 0.5 mL/min/g, P < 0.05) and were not different from each other (P = 0.30). Under left-anterior descending coronary stenosis, MBF increased in response to hypercapnia and adenosine (P < 0.05, all territories), but the effect was significantly lower than in the left-anterior descending coronary territory (with hypercapnia and adenosine; both P < 0.05). Mean perfusion defect volumes measured with adenosine and hypercapnia were significantly correlated (R = 0.85) and were not different (P = 0.12). After preadministration of caffeine, a known inhibitor of adenosine, resting MBF decreased; and hypercapnia increased MBF but not adenosine (P < 0.05). Conclusion: Arterial blood CO2 tension when increased by 25 mm Hg can induce MBF to the same level as a standard dose of adenosine. Prospectively targeted arterial CO2 has the capability to evolve as an alternative to current pharmacologic vasodilators used for cardiac stress testing.

3D high-resolution diffusion-weighted MRI at 3T: Preliminary application in prostate cancer patients undergoing active surveillance protocol for low-risk prostate cancer.

PURPOSE: To improve spatial resolution and image quality of diffusion-weighted (DW) MRI in detecting low-risk prostate cancer (lrPC) in patients undergoing active surveillance protocol (AS-PC), we propose the application of a diffusion-prepared balanced steady-state free precession (bSSFP) technique capable of multishot acquisition. METHODS: Diffusion-prepared bSSFP was compared with single-shot DW echo planar imaging (SS-DW-EPI) at two prescribed resolutions (2.1 × 2.1 × 3.5mm(3) , 0.9 × 0.9 × 3.5 mm(3) ) in nine healthy subjects and nine AS-PC patients. Geometric distortion and susceptibility artifacts were quantitatively assessed in all subjects. In AS-PC patients, lesion detection via blinded multiparametric MRI including T1-weighted, T2-weighted, dynamic contrast-enhanced imaging, and along with either of two DW methods were evaluated against 12-point biopsy. RESULTS: Geometric distortion and susceptibility artifacts were significantly less for diffusion-prepared bSSFP at both prescribed spatial resolutions than SS-DW-EPI. Apparent diffusion coefficients of healthy prostate tissue were concordant between the two DW methods at both spatial resolutions. In AS-PC patients, multiparametric MRI with diffusion-prepared bSSFP had greater sensitivity (94%, 63%), accuracy (76%, 67%), positive-predictive value (54%, 48%), negative-predictive value (97%, 82%), and area under the curve (0.80, 0.67) than with SS-DW-EPI. CONCLUSIONS: The proposed diffusion-prepared technique with higher spatial resolution and improved image quality over SS-DW-EPI resulted in better multiparametric MRI detection of lrPC in AS-PC patients.

Quantification of myocardial blood flow using non-electrocardiogram-triggered MRI with three-slice coverage.

PURPOSE: Accurate quantification of myocardial perfusion is dependent on reliable electrocardiogram (ECG) triggering. Measuring myocardial blood flow (MBF) in patients with arrhythmias or poor ECGs is currently infeasible with MR. The purpose of this study was to demonstrate the feasibility of a non-ECG-triggered method with clinically useful three-slice ventricular coverage for measurement of MBF in healthy volunteers. METHODS: A saturation recovery magnetization-prepared gradient recalled echo acquisition was continuously repeated during first-pass imaging. A slice-interleaved radial trajectory was employed to enable image-based retrospective triggering. The arterial input function was generated using a beat-by-beat T1 estimation method. The proposed technique was validated against a conventional ECG-triggered dual-bolus technique in 10 healthy volunteers. The technique was further demonstrated under adenosine stress in 12 healthy volunteers. RESULTS: The proposed method produced MBF with no significant difference compared with the ECG-triggered technique. The proposed method yielded mean myocardial perfusion reserve comparable to published literature. CONCLUSION: We have developed a non-ECG-triggered quantitative perfusion imaging method. In this preliminary study, our results demonstrate that our method yields comparable MBF compared with the conventional ECG-triggered method and that it is feasible for stress imaging.

Assessment of myocardial reactivity to controlled hypercapnia with free-breathing T2-prepared cardiac blood oxygen level-dependent MR imaging.

PURPOSE: To examine whether controlled and tolerable levels of hypercapnia may be an alternative to adenosine, a routinely used coronary vasodilator, in healthy human subjects and animals. MATERIALS AND METHODS: Human studies were approved by the institutional review board and were HIPAA compliant. Eighteen subjects had end-tidal partial pressure of carbon dioxide (PetCO2) increased by 10 mm Hg, and myocardial perfusion was monitored with myocardial blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. Animal studies were approved by the institutional animal care and use committee. Anesthetized canines with (n = 7) and without (n = 7) induced stenosis of the left anterior descending artery (LAD) underwent vasodilator challenges with hypercapnia and adenosine. LAD coronary blood flow velocity and free-breathing myocardial BOLD MR responses were measured at each intervention. Appropriate statistical tests were performed to evaluate measured quantitative changes in all parameters of interest in response to changes in partial pressure of carbon dioxide. RESULTS: Changes in myocardial BOLD MR signal were equivalent to reported changes with adenosine (11.2% ± 10.6 [hypercapnia, 10 mm Hg] vs 12% ± 12.3 [adenosine]; P = .75). In intact canines, there was a sigmoidal relationship between BOLD MR response and PetCO2 with most of the response occurring over a 10 mm Hg span. BOLD MR (17% ± 14 [hypercapnia] vs 14% ± 24 [adenosine]; P = .80) and coronary blood flow velocity (21% ± 16 [hypercapnia] vs 26% ± 27 [adenosine]; P > .99) responses were similar to that of adenosine infusion. BOLD MR signal changes in canines with LAD stenosis during hypercapnia and adenosine infusion were not different (1% ± 4 [hypercapnia] vs 6% ± 4 [adenosine]; P = .12). CONCLUSION: Free-breathing T2-prepared myocardial BOLD MR imaging showed that hypercapnia of 10 mm Hg may provide a cardiac hyperemic stimulus similar to adenosine.

Comparison of 3D free-breathing coronary MR angiography and 64-MDCT angiography for detection of coronary stenosis in patients with high calcium scores.

OBJECTIVE: The objective of our study was to compare the diagnostic performance of coronary MR angiography (MRA) and 64-MDCT angiography (MDCTA) for the detection of significant stenosis (> or = 50%) in patients with high calcium scores. MATERIALS AND METHODS: Eighteen patients (12 men, six women; mean age, 56 y; age range, 38-77 y) who had at least one calcified plaque with a calcium score of > 100 underwent coronary MRA and conventional coronary angiography (CAG) within 2 weeks of MDCTA. Coronary MRA image quality of the calcified segments was assessed by two observers in consensus on a 4-point scale (1 = not visible, 2 = poor, 3 = good, 4 = excellent) using a 10-segment model from the modified American Heart Association classification. Three experienced radiologists, unaware of the results of conventional CAG, independently assessed for the presence of significant stenosis on MDCTA images and the corresponding MRA images. Receiver operating characteristic (ROC) curves were calculated for each reader using conventional CAG as the gold standard. RESULTS: Thirty-three calcified plaques with a calcium score of > 100 were detected on MDCTA in the 18 patients. The coronary segments with nodal calcification (n = 17) showed a higher mean image quality score than the segments with diffuse calcification (n = 16) (3.47 +/- 0.62 vs 2.94 +/- 0.77, respectively; p < 0.05). Of the 33 coronary segments with calcification, 12 significant stenoses were identified on conventional CAG. The sensitivity, specificity, and area under the ROC curve (AUC) for MRA and MDCTA, respectively, were as follows: reader 1, 75%, 81%, 0.82 versus 75%, 48%, 0.68; reader 2, 83%, 71%, 0.82 versus 67%, 52%, 0.63; and reader 3, 83%, 71%, 0.85 versus 83%, 43%, 0.65, respectively. The average AUC of MRA for the three readers was significantly higher than that of MDCTA (p = 0.030). CONCLUSION: Coronary MRA has higher image quality for coronary segments with nodal calcification than for coronary segments with diffuse calcification. Coronary MRA has better diagnostic performance than coronary MDCTA for the detection of significant stenosis in patients with high calcium scores.

T2-prepared steady-state free precession blood oxygen level-dependent MR imaging of myocardial perfusion in a dog stenosis model.

PURPOSE: To assess the ability of a T2-prepared steady-state free precession blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging sequence to depict changes in myocardial perfusion during stress testing in a dog stenosis model. MATERIALS AND METHODS: Study was approved by the institutional Animal Care and Use Committee. A hydraulic occluder was placed in the left circumflex coronary artery (LCX) in 10 dogs. Adenosine was administered intravenously to increase coronary blood flow, and stenosis was achieved in the LCX with the occluder. A T2-prepared two-dimensional steady-state free precession sequence was used for BOLD imaging at a spatial resolution of 1.5 x 1.2 x 5.0 mm3, and first-pass perfusion images were acquired for visual comparison. Microspheres were injected to provide regional perfusion information. Mixed-effect regression analysis was performed to assess normalized MR signal intensity ratios and microsphere-measured perfusion differences. For the same data, 95% prediction intervals were calculated to determine the smallest perfusion change detectable. Means +/- standard deviations were calculated for myocardial regional comparison data. A two-tailed Student t test was used to determine if significant differences (P < .01) existed between different myocardial regions. RESULTS: Under maximal adenosine stress, MR clearly depicted stenotic regions and showed regional signal differences between the left anterior descending coronary artery (LAD)-fed myocardium and the stenosed LCX-fed myocardium. Visual comparisons with first-pass images were also excellent. Regional MR signal intensity differences between LAD and LCX-fed myocardium (1.24 +/- 0.08) were significantly different (P < .01) from differences between LAD and septal-fed myocardium (1.02 +/- 0.07), which was in agreement with microsphere-measured flow differences (LAD/LCX, 3.38 +/- 0.83; LAD/septal, 1.26 +/- 0.49). The linear mixed-effect regression model showed good correlation (R = 0.79) between MR differences and microsphere-measured flow differences. CONCLUSION: On T2-prepared steady-state free precession BOLD MR images in dogs, signal intensity differences were linearly related to flow differences in myocardium, with a high degree of correlation. SUPPLEMENTAL MATERIAL: radiology.rsnajnls.org/cgi/content/full/236/2/503/DC1

Alpha-galactosidase A deficiency accelerates atherosclerosis in mice with apolipoprotein E deficiency.

BACKGROUND: Alpha-galactosidase A (Gla) deficiency leads to widespread tissue accumulation of neutral glycosphingolipids and is associated with premature vascular complications such as myocardial infarction and stroke. Glycosphingolipids have been shown to accumulate in human atherosclerotic lesions, although their role in atherogenesis is unclear. METHODS AND RESULTS: To determine whether Gla affects the progression of atherosclerosis, mice were generated with combined deficiencies of apolipoprotein E and Gla. At 45 weeks of age, Gla-deficient mice had developed more atherosclerosis than mice with normal Gla expression (25.1+/-14.0 versus 12.3+/-9.3 mm2 of total lesion area, P<0.02). This increase in atherosclerosis was associated with the presence of increased Gb3, enhanced inducible nitric oxide synthase expression, and increased nitrotyrosine staining. CONCLUSIONS: These findings suggest that deficiency of Gla leads to increased inducible nitric oxide synthase expression and accelerated atherosclerosis.