Cardiac MRI at Low Field Strengths.

Cardiac MR imaging is well established for assessment of cardiovascular structure and function, myocardial scar, quantitative flow, parametric mapping, and myocardial perfusion. Despite the clear evidence supporting the use of cardiac MRI for a wide range of indications, it is underutilized clinically. Recent developments in low-field MRI technology, including modern data acquisition and image reconstruction methods, are enabling high-quality low-field imaging that may improve the cost-benefit ratio for cardiac MRI. Studies to-date confirm that low-field MRI offers high measurement concordance and consistent interpretation with clinical imaging for several routine sequences. Moreover, low-field MRI may enable specific new clinical opportunities for cardiac imaging such as imaging near metal implants, MRI-guided interventions, combined cardiopulmonary assessment, and imaging of patients with severe obesity. In this review, we discuss the recent progress in low-field cardiac MRI with a focus on technical developments and early clinical validation studies. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Two-center validation of Pilot Tone based cardiac triggering of a comprehensive cardiovascular magnetic resonance examination.

The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established. To evaluate the performance of PTC triggering in a comprehensive CMR exam. Fifteen volunteers and 20 patients were recruited at two centers. ECG triggered images were collected for comparison in a subset of sequences. The PTC trigger accuracy was evaluated against ECG in cine acquisitions. Two experienced readers scored image quality in PTC-triggered cine, late gadolinium enhancement (LGE), and T1- and T2-weighted dark-blood turbo spin echo (DB-TSE) images. Quantitative cardiac function, flow, and parametric mapping values obtained using PTC and ECG triggered sequences were compared. Breath-held segmented cine used for trigger timing analysis was collected in 15 volunteers and 14 patients. PTC calibration failed in three volunteers and one patient; ECG trigger recording failed in one patient. Out of 1987 total heartbeats, three mismatched trigger PTC-ECG pairs were found. Image quality scores showed no significant difference between PTC and ECG triggering. There was no significant difference found in quantitative measurements in volunteers. In patients, the only significant difference was found in post-contrast T1 (p = 0.04). ICC showed moderate to excellent agreement in all measurements. PTC performance was equivalent to ECG in terms of triggering consistency, image quality, and quantitative image measurements across multiple CMR applications.

Two-center validation of Pilot Tone Based Cardiac Triggering of a Comprehensive Cardiovascular Magnetic Resonance Examination.

Background: The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established. Purpose: To evaluate the performance of PTC triggering in a comprehensive CMR exam. Methods: Fifteen volunteers and twenty patients were recruited at two centers. ECG triggered images were collected for comparison in a subset of sequences. The PTC trigger accuracy was evaluated against ECG in cine acquisitions. Two experienced readers scored image quality in PTC-triggered cine, late gadolinium enhancement (LGE), and T1- and T2-weighted dark-blood turbo spin echo (DB-TSE) images. Quantitative cardiac function, flow, and parametric mapping values obtained using PTC and ECG triggered sequences were compared. Results: Breath-held segmented cine used for trigger timing analysis was collected in 15 volunteers and 14 patients. PTC calibration failed in three volunteers and one patient; ECG trigger recording failed in one patient. Out of 1987 total heartbeats, three mismatched trigger PTC-ECG pairs were found. Image quality scores showed no significant difference between PTC and ECG triggering. There was no significant difference found in quantitative measurements in volunteers. In patients, the only significant difference was found in post-contrast T1 (p = 0.04). ICC showed moderate to excellent agreement in all measurements. Conclusion: PTC performance was equivalent to ECG in terms of triggering consistency, image quality, and quantitative image measurements across multiple CMR applications.

"Nurse-The Archer" Fighting Against the Hidden Enemy.

Background and aim: The coronavirus disease-2019 (COVID-19) pandemic is a global threat spreading like a wildfire and taking the world by its storm. It has challenged the healthcare delivery systems and disrupted them in a way no one ever imagined before. We at Apollo Hospitals, Chennai, Tamil Nadu, India received many patients in the COVID critical care unit (CCU) and found a gradual lack of bundle care compliance resulting in an upsurge of central line-associated bloodstream infection (CLABSI) amid the patients. Materials and methods: A qualitative research approach and quasi-experimental research design were selected to assess the knowledge of the 150 frontline COVID CCU nurses regarding the CLABSI bundle and its prevention strategies. Results: This study revealed that 57% [mean (M) = 12.6; standard deviation (SD) = 2.37] of nurses had inadequate knowledge of the CLABSI bundle and its prevention strategies, in the pretest and scored 80% (M = 6.7; SD = 2.28) in the post-test, with "t" = 22.06 at p < 0.00001 after the hands-on training. The percentage of compliance to CLABSI bundle care increased to 83% and thereafter in an increasing trend. This was clearly evident through the reduction in the preventable CLABSI rate among critically ill COVID-19 patients. Conclusion: Nurses are on the frontline in preventing and controlling healthcare-associated infections (HAIs). Fighting with all the visible and invisible challenges, our research focused on hands-on training for frontline warriors to adhere to the CLABSI bundle care which drove us to the reduction in preventable CLABSI rate in our hospital through improved CLABSI bundle compliance. How to cite this article: Premkumar S, Ramanathan Y, Varghese JJ, Morris B, Nambi PS, Ramakrishnan N, et al. "Nurse-The Archer" Fighting Against the Hidden Enemy. Indian J Crit Care Med 2023;27(4):246-253.

Parametric mapping by cardiovascular magnetic resonance imaging in sudden cardiac arrest survivors.

Etiology of sudden cardiac arrest (SCA) is identified in less than 30% of survivors without coronary artery disease. We sought to assess the diagnostic role of myocardial parametric mapping using cardiovascular magnetic resonance (CMR) in identifying SCA etiology. Consecutive SCA survivors undergoing CMR with myocardial parametric mapping were included in the study. The determination if CMR was decisive or contributory in identifying SCA etiology was made if the diagnosis was unclear prior to CMR, and the discharge diagnosis was consistent with the CMR result. Parametric mapping was considered essential for establishing probable SCA etiology by CMR if the SCA cause could not have been determined without its utilization. If the CMR diagnosis could have been potentially based on the combination of cine and LGE imaging, parametric mapping was considered contributory. Of the 35 patients (mean age 46.9 ± 14.1 years; 57% males) included, SCA diagnosis was based on CMR in 23 (66%) patients. Of those, parametric mapping was essential for the diagnosis of myocarditis and tako-tsubo cardiomyopathy (11/48%) and contributed to the diagnosis in 10 (43%) additional cases. Inclusion of quantitative T1 and T2 parametric mapping in the SCA CMR protocol has the potential to increase diagnostic yield of CMR and further specify SCA etiology, especially myocarditis.

Cardiac magnetic resonance imaging for left atrial appendage closure planning.

BACKGROUND: Transesophageal echocardiography (TEE) and cardiac computed tomography angiography (CCTA) are currently utilized for left atrial appendage closure (LAAC) planning. During the recent global iodine contrast media shortage in 2022, cardiac magnetic resonance imaging (CMR) was utilized for the first time for LAAC planning. This study sought to assess the utility of CMR versus TEE for LAAC planning. METHODS: This single center retrospective study consisted of all patients who underwent preoperative CMR for LAAC with Watchman FLX or Amplatzer Amulet. Key measures were accuracy of LAA thrombus exclusion, ostial diameter, depth, lobe count, morphology, accuracy of predicted device size, and devices deployed per case. Bland-Altman Analysis was used to compare CMR versus TEE measurements of LAA ostial diameter and depth. RESULTS: 25 patients underwent preoperative CMR for LAAC planning. A total of 24 (96%) cases were successfully completed with 1.2 ± 0.5 devices deployed per case. Among the 18 patients who underwent intraoperative TEE, there was no significant difference between CMR versus TEE in LAA thrombus exclusion (CMR 83% vs. TEE 100% cases, p = .229), lobe count (CMR 1.7 ± 0.8 vs. TEE 1.4 ± 0.6, p = .177), morphology (p = .422), and accuracy of predicted device size (CMR 67% vs. TEE 72% cases, p = 1.000). When comparing the difference between CMR and TEE measurements, Bland-Altman analysis demonstrated no significant difference in LAA ostial diameter (CMR-TEE bias 0.7 mm, 95% CI [-1.1, 2.4], p = .420), but LAA depth was significantly larger with CMR versus TEE (CMR-TEE bias 7.4 mm, 95% CI [1.6, 13.2], p = .015). CONCLUSIONS: CMR is a promising alternative for LAAC planning in cases where TEE or CCTA are contraindicated or unavailable.

Building a comprehensive cardiovascular magnetic resonance exam on a commercial 0.55 T system: A pictorial essay on potential applications.

Background: Contemporary advances in low-field magnetic resonance imaging systems can potentially widen access to cardiovascular magnetic resonance (CMR) imaging. We present our initial experience in building a comprehensive CMR protocol on a commercial 0.55 T system with a gradient performance of 26 mT/m amplitude and 45 T/m/s slew rate. To achieve sufficient image quality, we adapted standard imaging techniques when possible, and implemented compressed-sensing (CS) based techniques when needed in an effort to compensate for the inherently low signal-to-noise ratio at lower field strength. Methods: A prototype CMR exam was built on an 80 cm, ultra-wide bore commercial 0.55 T MR system. Implementation of all components aimed to overcome the inherently lower signal of low-field and the relatively longer echo and repetition times owing to the slower gradients. CS-based breath-held and real-time cine imaging was built utilizing high acceleration rates to meet nominal spatial and temporal resolution recommendations. Similarly, CS 2D phase-contrast cine was implemented for flow. Dark-blood turbo spin echo sequences with deep learning based denoising were implemented for morphology assessment. Magnetization-prepared single-shot myocardial mapping techniques incorporated additional source images. CS-based dynamic contrast-enhanced imaging was implemented for myocardial perfusion and 3D MR angiography. Non-contrast 3D MR angiography was built with electrocardiogram-triggered, navigator-gated magnetization-prepared methods. Late gadolinium enhanced (LGE) tissue characterization methods included breath-held segmented and free-breathing single-shot imaging with motion correction and averaging using an increased number of source images. Proof-of-concept was demonstrated through porcine infarct model, healthy volunteer, and patient scans. Results: Reasonable image quality was demonstrated for cardiovascular structure, function, flow, and LGE assessment. Low-field afforded utilization of higher flip angles for cine and MR angiography. CS-based techniques were able to overcome gradient speed limitations and meet spatial and temporal resolution recommendations with imaging times comparable to higher performance scanners. Tissue mapping and perfusion imaging require further development. Conclusion: We implemented cardiac applications demonstrating the potential for comprehensive CMR on a novel commercial 0.55 T system. Further development and validation studies are needed before this technology can be applied clinically.

T2 mapping in myocardial disease: a comprehensive review.

Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for myocardial tissue characterization. Elevated transverse relaxation time (T2) is specific for increased myocardial water content, increased free water, and is used as an index of myocardial edema. The strengths of quantitative T2 mapping lie in the accurate characterization of myocardial edema, and the early detection of reversible myocardial disease without the use of contrast agents or ionizing radiation. Quantitative T2 mapping overcomes the limitations of T2-weighted imaging for reliable assessment of diffuse myocardial edema and can be used to diagnose, stage, and monitor myocardial injury. Strong evidence supports the clinical use of T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy. Accumulating data support the utility of T2 mapping for the assessment of other cardiomyopathies, rheumatologic conditions with cardiac involvement, and monitoring for cancer therapy-related cardiac injury. Importantly, elevated T2 relaxation time may be the first sign of myocardial injury in many diseases and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. This comprehensive review discusses the technical considerations and clinical roles of myocardial T2 mapping with an emphasis on expanding the impact of this unique, noninvasive tissue parameter.

Prevalence and haemodynamic profiles of pulmonary hypertension in cardiac amyloidosis.

OBJECTIVES: While cardiac amyloidosis (CA) classically involves the left ventricle (LV), less is known about its impact on the right ventricle (RV) and pulmonary vasculature. We performed a retrospective analysis to identify the prevalence and types of pulmonary hypertension (PH) profiles in CA and to determine haemodynamic and cardiovascular magnetic resonance (CMR) predictors of major adverse cardiovascular events (MACE). METHODS: Patients with CA who underwent CMR and right heart catheterisation (RHC) within 1 year between 2010 and 2019 were included. Patients were assigned the following haemodynamic profiles based on RHC: no PH, precapillary PH, isolated postcapillary PH (IPCPH), or combined precapillary and postcapillary PH (CPCPH). The relationship between PH profile and MACE (death, heart failure hospitalisation) was assessed using survival analysis. CMR and RV parameters were correlated with MACE using Cox-regression analysis. RESULTS: A total of 52 patients were included (age 69±9 years, 85% men). RHC was performed during biopsy in 44 (85%) and for clinical indications in 8 (15%) patients. Rates of no PH, precapillary PH, IPCPH and CPCPH were 5 (10%), 3 (6%), 29 (55%) and 15 (29%), respectively. Haemodynamic PH profile did not correlate with risk of death (p=0.98) or MACE (p=0.67). Transpulmonary gradient (TPG) (HR 0.88, CI 0.80 to 0.97), RV, (HR 0.95, CI 0.92 to 0.98) and LV ejection fraction (HR 0.95, CI 0.92 to 0.98) were significantly associated with MACE. CONCLUSIONS: PH is highly prevalent in CA, even at the time of diagnosis. While IPCPH was most common, CPCPH is not infrequent. TPG and RV ejection fraction (RVEF) are prognostic markers in this population.

Prospective correction of patient-specific respiratory motion in myocardial T1 and T2 mapping.

PURPOSE: Respiratory motion in cardiovascular MRI presents a challenging problem with many potential solutions. Current approaches require breath-holds, apply retrospective image registration, or significantly increase scan time by respiratory gating. Myocardial T1 and T2 mapping techniques are particularly sensitive to motion as they require multiple source images to be accurately aligned prior to the estimation of tissue relaxation. We propose a patient-specific prospective motion correction (PROCO) strategy that corrects respiratory motion on the fly with the goal of reducing the spatial variation of myocardial parametric mapping techniques. METHODS: A rapid, patient-specific training scan was performed to characterize respiration-induced motion of the heart relative to a diaphragmatic navigator, and a parametric mapping pulse sequence utilized the resulting motion model to prospectively update the scan plane in real-time. Midventricular short-axis T1 and T2 maps were acquired under breath-hold or free-breathing conditions with and without PROCO in 7 healthy volunteers and 3 patients. T1 and T2 were measured in 6 segments and compared to reference standard breath-hold measurements using Bland-Altman analysis. RESULTS: PROCO significantly reduced the spatial variation of parametric maps acquired during free-breathing, producing limits of agreement of -47.16 to 30.98 ms (T1 ) and -1.35 to 4.02 ms (T2 ), compared to -67.77 to 74.34 ms (T1 ) and -2.21 to 5.62 ms (T2 ) for free-breathing acquisition without PROCO. CONCLUSION: Patient-specific respiratory PROCO method significantly reduced the spatial variation of myocardial T1 and T2 mapping, while allowing for 100% efficient free-breathing acquisitions.

Patient-Adaptive Magnetic Resonance Oximetry: Comparison With Invasive Catheter Measurement of Blood Oxygen Saturation in Patients With Cardiovascular Disease.

BACKGROUND: The current standard method to measure intracardiac oxygen (O2 ) saturation is by invasive catheterization. Accurate noninvasive blood O2 saturation by MRI could potentially reduce the duration and risk of invasive diagnostic procedures. PURPOSE: To noninvasively determine blood oxygen saturation in the heart with MRI and compare the accuracy with catheter measurements. STUDY TYPE: Prospective. SUBJECTS: Thirty-two patients referred for right heart catheterization (RHC) and five healthy subjects. FIELD STRENGTH/SEQUENCE: T2-prepared single-shot balanced steady-state free-precession at 1.5T. ASSESSMENT: MR signals in venous and arterial blood, hematocrit, and arterial O2 saturation from a pulse oximeter were jointly processed to fit the Luz-Meiboom model and estimate blood O2 saturation in the right heart. Interstudy reproducibility was evaluated in volunteers and patients. Interobserver reproducibility among three readers was assessed using data from volunteers and 10 patients. Accuracy of MR oximetry was compared to RHC in all patients. STATISTICAL TESTS: Coefficient of variation, intraclass correlation coefficient, Bland-Altman analysis, Pearson's correlation. RESULTS: The coefficient of variation for interstudy reproducibility of O2 saturation was 2.6% on average in volunteers and 3.2% in patients. Interobserver reproducibility among three observers yielded intraclass correlation coefficients of 0.81 and 0.87 respectively for RV and MPA O2 saturation. O2 saturation (y = 0.85x + 0.13, R = 0.78) and (a-v)O2 difference (y = 0.71x + 0.90, R = 0.69) by MR and RHC were significantly correlated (N = 32, P < 0.05 in both cases) in patients. MR slightly overestimated O2 saturation compared to RHC with 2% ± 5% bias and limits of agreement between -7% and 12%. DATA CONCLUSION: MR oximetry is repeatable and reproducible. Good agreement was shown between MR and catheter venous O2 saturation and (a-v)O2 difference in a cohort whose venous O2 ranged from abnormally low to high levels, with most values in the normal physiological range. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Assessment of cardiac function, blood flow and myocardial tissue relaxation parameters at 0.35 T.

A low field strength (B0) system could increase cardiac MRI availability for patients otherwise contraindicated at higher field. Lower equipment costs could also broaden cardiac MR accessibility. The current study investigated the feasibility of cardiac function with steady-state free precession and flow assessment with phase contrast (PC) cine images at 0.35 T, and evaluated differences in myocardial relaxation times using quantitative T1, T2 and T2* maps by comparison with 1.5 and 3 T results in a small cohort of six healthy volunteers. Signal-to-noise ratio (SNR) differences across systems were characterized with proton density-weighted spin echo phantom data. SNR at 0.35 T was lower by factors of 5.5 and 15.0 compared with the 1.5 and 3 T systems used in this study. All cine images at 0.35 T scored 3 or greater on a five-point image quality scale. Normalized blood-myocardium contrast in cine images, left ventricular volumes (end diastolic volume, end systolic volume) and function (ejection fraction and stroke volume) measures at 0.35 T matched 1.5 and 3 T results. Phase-to-noise ratio in 0.35 T PC images (11.7 ± 1.9) was lower than 1.5 T (18.7 ± 5.2) and 3 T (44.9 ± 16.5). Peak velocity and stroke volume determined from PC images were similar across systems. Myocardial T1 increased (564 ± 13 ms at 0.35 T, 955 ± 19 ms at 1.5 T and 1200 ± 35 ms at 3 T) while T2 (59 ± 4 ms at 0.35 T, 49 ± 3 ms at 1.5 T and 40 ± 2 ms at 3 T) and T2* (42 ± 8 ms at 0.35 T, 33 ± 6 ms at 1.5 T and 24 ± 3 ms at 3 T) decreased with increasing B0. Despite SNR deficits, cardiovascular function, flow assessment and myocardial relaxation parameter mapping is feasible at 0.35 T using standard cardiovascular imaging sequences.

CMR-based blood oximetry via multi-parametric estimation using multiple T2 measurements.

BACKGROUND: Measurement of blood oxygen saturation (O2 saturation) is of great importance for evaluation of patients with many cardiovascular diseases, but currently there are no established non-invasive methods to measure blood O2 saturation in the heart. While T2-based CMR oximetry methods have been previously described, these approaches rely on technique-specific calibration factors that may not generalize across patient populations and are impractical to obtain in individual patients. We present a solution that utilizes multiple T2 measurements made using different inter-echo pulse spacings. These data are jointly processed to estimate all unknown parameters, including O2 saturation, in the Luz-Meiboom (L-M) model. We evaluated the accuracy of the proposed method against invasive catheterization in a porcine hypoxemia model. METHODS: Sufficient data diversity to estimate the various unknown parameters of the L-M model, including O2 saturation, was achieved by acquiring four T2 maps, each at a different τ 180 (12, 15, 20, and 25 ms). Venous and arterial blood T2 values from these maps, together with hematocrit and arterial O2 saturation, were jointly processed to derive estimates for venous O2 saturation and other nuisance parameters in the L-M model. The technique was validated by a progressive graded hypoxemia experiment in seven pigs. CMR estimates of O2 saturation in the right ventricle were compared against a reference O2 saturation obtained by invasive catheterization from the right atrium in each pig, at each hypoxemia stage. O2 saturation derived from the proposed technique was also compared against the previously described method of applying a global calibration factor (K) to the simplified L-M model. RESULTS: Venous O2 saturation results obtained using the proposed CMR oximetry method exhibited better agreement (y = 0.84× + 12.29, R2 = 0.89) with invasive blood gas analysis when compared to O2 saturation estimated by a global calibration method (y = 0.69× + 27.52, R2 = 0.73). CONCLUSIONS: We have demonstrated a novel, non-invasive method to estimate O2 saturation using quantitative T2 mapping. This technique may provide a valuable addition to the diagnostic utility of CMR in patients with congenital heart disease, heart failure, and pulmonary hypertension.

Cardiopulmonary exercise testing in the MRI environment.

Maximal oxygen consumption ([Formula: see text]max) measured by cardiopulmonary exercise testing (CPX) is the gold standard for assessment of cardiorespiratory fitness. Likewise, cardiovascular magnetic resonance (CMR) is the gold standard for quantification of cardiac function. The combination of CPX and CMR may offer unique insights into cardiopulmonary pathophysiology; however, the MRI-compatible equipment needed to combine these tests has not been available to date. We sought to determine whether CPX testing in the MRI environment, using equipment modified for MRI yields results equivalent to those obtained in standard exercise physiology (EP) lab. Ten recreationally trained subjects completed [Formula: see text]max tests in different locations; an EP laboratory and an MRI laboratory, using site specific equipment. CMR cine images of the heart were acquired before and immediately after maximal exercise to measure cardiac function. Subjects in all tests met criteria indicating that peak exercise was achieved. Despite equipment modifications for the MRI environment, [Formula: see text]max was nearly identical between tests run in the different labs (95% lower confidence limit (LCL) = 0.8182). The mean difference in [Formula: see text]max was less than 3.40 ml (kg/min)(-1), within the variability expected for tests performed on different days, in different locations, using different metabolic carts. MRI performed at rest and following peak exercise stress indicated cardiac output increased from 5.1 ± 1.0 l min(-1) to 16.4 ± 5.6 l min(-1), LVEF increased from 65.2 ± 3.3% to 78.4 ± 4.8%, while RVEF increased from 52.8 ± 5.3% to 63.4 ± 5.3%. Regression analysis revealed a significant positive correlation between [Formula: see text]max and stroke volume (R = 0.788, P = 0.006), while the correlation with cardiac output did not reach statistical significance (R = 0.505, P = 0.137). [Formula: see text]max CPX testing can be effectively performed in the MRI environment, enabling direct combination of physiological data with advanced post-exercise imaging in the same test session.

Rapid assessment of quantitative T1, T2 and T2* in lower extremity muscles in response to maximal treadmill exercise.

MRI provides a non-invasive diagnostic platform to quantify the physical and physiological attributes of skeletal muscle at rest and in response to exercise. MR relaxation parameters (T1, T2 and T2*) are characteristic of tissue composition and metabolic properties. With the recent advent of quantitative techniques that allow rapid acquisition of T1, T2 and T2* maps, we posited that an integrated treadmill exercise-quantitative relaxometry paradigm can rapidly characterize exercise-induced changes in skeletal muscle relaxation parameters. Accordingly, we investigated the rest/recovery kinetics of T1, T2 and T2* in response to treadmill exercise in the anterior tibialis, soleus and gastrocnemius muscles of healthy volunteers, and the relationship of these parameters to age and gender. Thirty healthy volunteers (50.3 ± 16.6 years) performed the Bruce treadmill exercise protocol to maximal exhaustion. Relaxometric maps were sequentially acquired at baseline and for approximately 44 minutes post-exercise. Our results show that T1, T2 and T2* are significantly and differentially increased immediately post-exercise among the leg muscle groups, and these values recover to near baseline within 30-44 minutes. Our results demonstrate the potential to characterize the kinetics of relaxation parameters with quantitative mapping and upright exercise, providing normative values and some clarity on the impact of age and gender.

Reproducibility of thoracic and abdominal aortic wall measurements with three-dimensional, variable flip angle (SPACE) MRI.

PURPOSE: To evaluate the reproducibility and repeatability of high-resolution, isotropic thoracic and abdominal aortic wall measurements, and determine the implications they have on the number of subjects necessary for future clinical trials. MATERIALS AND METHODS: Using a T1-weighted three-dimensional MRI SPACE sequence, we evaluated the interobserver, intraobserver, and scan-rescan variability of isotropic thoracic and abdominal aortic wall measurements in 15 cardiovascular diseased patients and 6 normal volunteers. Main outcome analyses were intracorrelation coefficient (ICC), mean relative error (mRE), and sample size calculation at 80% power to be used to compare placebo group and treatment group means in future two-arm randomized clinical trials. RESULTS: Excellent reliability, ICC > 0.8 (P < 0.001) and small mRE < 10% were demonstrated for the interobserver, intraobserver, and scan-rescan variability for all investigated measures: lumen area (LA), outer wall area (OWA), wall area (VWA), total wall volume (TWV), and percentage wall volume (%WV). Sample size calculation revealed slightly different sample size per treatment arm for thoracic and abdominal aorta segments (maximum number of subjects: 352 subjects for thoracic segment versus 421 subjects for abdominal segment for LA at 5% difference, and minimum of 3 thoracic versus 4 abdominal subjects needed for %WV evaluation at 25% difference). CONCLUSION: Our study demonstrates the reproducibility and repeatability of SPACE aortic plaque measurements, and gives insight into the number of subjects needed for the design of therapeutic studies in aortic atherosclerosis.

Aliskiren effect on plaque progression in established atherosclerosis using high resolution 3D MRI (ALPINE): a double-blind placebo-controlled trial.

BACKGROUND: The renin-angiotensin system is well recognized as a mediator of pathophysiological events in atherosclerosis. The benefits of renin inhibition in atherosclerosis, especially when used in combination with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are currently not known. We hypothesized that treatment with the renin inhibitor aliskiren in patients with established cardiovascular disease will prevent the progression of atherosclerosis as determined by high-resolution magnetic resonance imaging (MRI) measurements of arterial wall volume in the thoracic and abdominal aortas of high-risk patients with preexisting cardiovascular disease. METHODS AND RESULTS: This was a single-center, randomized, double-blind, placebo-controlled trial in patients with established cardiovascular disease. After a 2-week single-blind placebo phase, patients were randomized to receive either placebo (n=37, mean ± SD age 64.5 ± 8.9 years, 3 women) or 150 mg of aliskiren (n=34, mean ± SD age 63.9 ± 11.5 years, 9 women). Treatment dose was escalated to 300 mg at 2 weeks and maintained during the remainder of the study. Patients underwent dark-blood, 3-dimensional MRI assessment of atherosclerotic plaque in the thoracic and abdominal segments at baseline and on study completion or termination (up to 36 weeks of drug or matching placebo). Aliskiren use resulted in significant progression of aortic wall volume (normalized total wall volume 5.31 ± 6.57 vs 0.15 ± 4.39 mm(3), P=0.03, and percentage wall volume 3.37 ± 2.96% vs 0.97 ± 2.02%, P=0.04) compared with placebo. In a subgroup analysis of subjects receiving ACEI/ARB therapy, atherosclerosis progression was observed only in the aliskiren group, not in the placebo group. CONCLUSIONS: MRI quantification of atheroma plaque burden demonstrated that aliskiren use in patients with preexisting cardiovascular disease resulted in an unexpected increase in aortic atherosclerosis compared with placebo. Although preliminary, these results may have implications for the use of renin inhibition as a therapeutic strategy in patients with cardiovascular disease, especially in those receiving ACEI/ARB therapy. CLINICAL TRIAL REGISTRATION: URL: http://ClinicalTrials.gov Unique identifier: NCT01417104.