Myocardial Strain for the Differentiation of Myocardial Involvement in the Post-Acute Sequelae of COVID-19-A Multiparametric Cardiac MRI Study.

Myocardial involvement was shown to be associated with an unfavorable prognosis in patients with COVID-19, which could lead to fatal outcomes as in myocardial injury-induced arrhythmias and sudden cardiac death. We hypothesized that magnetic resonance imaging (MRI) myocardial strain parameters are sensitive markers for identifying subclinical cardiac dysfunction associated with myocardial involvement in the post-acute sequelae of COVID-19 (PASC). This study evaluated 115 subjects, including 65 consecutive COVID-19 patients, using MRI for the assessment of either post-COVID-19 myocarditis or other cardiomyopathies. Subjects were categorized, based on the results of the MRI exams, as having either 'suspected' or 'excluded' myocarditis. A control group of 50 matched individuals was studied. Along with parameters of global cardiac function, the MRI images were analyzed for measurements of the myocardial T1, T2, extracellular volume (ECV), strain, and strain rate. Based on the MRI late gadolinium enhancement and T1/T2/ECV mappings, myocarditis was suspected in 7 out of 22 patients referred due to concern of myocarditis and in 9 out of 43 patients referred due to concern of cardiomyopathies. The myocardial global longitudinal, circumferential, and radial strains and strain rates in the suspected myocarditis group were significantly smaller than those in the excluded myocarditis group, which in turn were significantly smaller than those in the control group. The results showed significant correlations between the strain, strain rate, and global cardiac function parameters. In conclusion, this study emphasizes the value of multiparametric MRI for differentiating patients with myocardial involvement in the PASC based on changes in the myocardial contractility pattern and tissue structure.

2nd Window NIR Imaging of Radiation Injury Mitigation Provided by Reduced Notch-Dll4 Expression on Vasculature.

PURPOSE: Vascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100 nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney. PROCEDURES: Consomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11-12 weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13 Gy partial body irradiation at 42- and 90 days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection. RESULTS: We show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction. CONCLUSIONS: Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney.

Profibrotic COVID-19 subphenotype exhibits enhanced localized ER-dependent HSP47+ expression in cardiac myofibroblasts in situ.

We recently described a subgroup of autopsied COVID-19 subjects (∼40%), termed 'profibrotic phenotype,' who exhibited clusters of myofibroblasts (Mfbs), which were positive for the collagen-specific chaperone heat shock protein 47 (HSP47+) in situ. This report identifies increased, localized (hot spot restricted) expression of αSMA, COLα1, POSTN and FAP supporting the identity of HSP47+ cells as myofibroblasts and characterizing a profibrotic extracellular matrix (ECM) phenotype. Coupled with increased GRP78 in COVID-19 subjects, these data could reflect induction of the unfolded protein response for mitigation of proteostasis (i.e., protein homeostasis) dysfunction in discrete clusters of cells. ECM shifts in selected COVID-19 subjects occur without significant increases in either global trichrome positive staining or myocardial injury based quantitively on standard H&E scoring. Our findings also suggest distinct mechanism(s) for ECM remodeling in the setting of SARS-CoV-2 infection. The ratio of CD163+/CD68+ cells is increased in hot spots of profibrotic hearts compared with either controls or outside of hot spots in COVID-19 subjects. In sum, matrix remodeling of human COVID-19 hearts in situ is characterized by site-restricted profibrotic mediated (e.g., HSP47+ Mfbs, CD163+ Mφs) modifications in ECM (i.e., COLα1, POSTN, FAP), with a strong correlation between COLα1 and HSP47+cells within hot spots. Given the established associations of viral infection (e.g., human immunodeficiency virus; HIV), myocardial fibrosis and sudden cardiac death, early screening tools (e.g., plasma biomarkers, noninvasive cardiac magnetic resonance imaging) for diagnosis, monitoring and treatment of fibrotic ECM remodeling are warranted for COVID-19 high-risk populations.

Real-Time Strain-Encoding Cardiovascular MRI for Assessment of Regional Heart Function in Tetralogy of Fallot Patients.

BACKGROUND: Tetralogy of Fallot (ToF) is the most common form of cyanotic congenital heart disease, where right ventricular (RV) function is an important determinant of subsequent intervention. OBJECTIVE: In this study, we evaluate the feasibility of fast strain-encoding (fastSENC; a one-heartbeat sequence) magnetic resonance imaging (MRI) for assessing regional cardiac function in ToF. METHOD: FastSENC was implemented to characterize regional circumferential (Ecc) and longitudinal (Ell) strains in the left ventricle (LV) and RV in post-repair ToF. Data analysis was conducted to compare strain measurements in the RV to those in the LV, as well as to those generated by the MRI Tissue-Tracking (MRI-TT) technique, and to assess the relationship between strain and ejection fraction (EF). RESULTS: Despite normal LVEF (55±8.5%), RVEF was borderline (46±6.4%), but significantly lower than LVEF. RV strains (RV-Ell=-20.2±2.9%, RV-Ecc=-15.7±6.4%) were less than LV strains (LV-Ell=-21.7±3.7%, LV-Ecc=-18.3±4.7%), and Ell was the dominant strain component. Strain differences between fastSENC and MRI-TT were less significant in RV than in LV. There existed moderate and weak correlations for RV-Ecc and RV-Ell, respectively, against RVEF. Compared to LV strain, RV strain showed regional heterogeneity with a trend for reduced strain from the inferior to anterior regions. Inter-ventricular strain delay was larger for Ell (64±47ms) compared to Ecc (36±40ms), reflecting a trend for contraction dyssynchrony. CONCLUSION: FastSENC allows for characterizing subclinical regional RV dysfunction in ToF. Due to its sensitivity for evaluating regional myocardial contractility patterns and real-time imaging capability without the need for breath-holding, fastSENC makes it more suitable for evaluating RV function in ToF.

Aortic Remodeling Kinetics in Response to Coarctation-Induced Mechanical Perturbations.

Background: Coarctation of the aorta (CoA; constriction of the proximal descending thoracic aorta) is among the most common congenital cardiovascular defects. Coarctation-induced mechanical perturbations trigger a cycle of mechano-transduction events leading to irreversible precursors of hypertension including arterial thickening, stiffening, and vasoactive dysfunction in proximal conduit arteries. This study sought to identify kinetics of the stress-mediated compensatory response leading to these alterations using a preclinical rabbit model of CoA. Methods: A prior growth and remodeling (G&R) framework was reformulated and fit to empirical measurements from CoA rabbits classified into one control and nine CoA groups of various severities and durations (n = 63, 5-11/group). Empirical measurements included Doppler ultrasound imaging, uniaxial extension testing, catheter-based blood pressure, and wire myography, yielding the time evolution of arterial thickening, stiffening, and vasoactive dysfunction required to fit G&R constitutive parameters. Results: Excellent agreement was observed between model predictions and observed patterns of arterial thickening, stiffening, and dysfunction among all CoA groups. For example, predicted vascular impairment was not significantly different from empirical observations via wire myography (p-value > 0.13). Specifically, 48% and 45% impairment was observed in smooth muscle contraction and endothelial-dependent relaxation, respectively, which were accurately predicted using the G&R model. Conclusions: The resulting G&R model, for the first time, allows for prediction of hypertension precursors at neonatal ages that is currently challenging to examine in preclinical models. These findings provide a validated computational tool for prediction of persistent arterial dysfunction and identification of revised severity-duration thresholds that may ultimately avoid hypertension from CoA.

Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation in a preclinical model.

Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. CoA patients frequently undergo surgical repair, but hypertension (HTN) is still common. The current treatment guideline has revealed irreversible changes in structure and function, yet revised severity guidelines have not been proposed. Our objective was to quantify temporal alterations in mechanical stimuli and changes in arterial geometry in response to the range of CoA severities and durations (i.e. age of treatment) seen clinically. Rabbits were exposed to CoA resulting in peak-to-peak blood pressure gradient (BPGpp) severities of ≤ 10, 10-20, and ≥ 20 mmHg for a duration of ~ 1, 3, or 20 weeks using permanent, dissolvable, and rapidly dissolvable sutures. Elastic moduli and thickness were estimated from imaging and longitudinal fluid-structure interaction (FSI) simulations were conducted at different ages using geometries and boundary conditions from experimentally measured data. Mechanical stimuli were characterized including blood flow velocity patterns, wall tension, and radial strain. Experimental results show vascular alternations including thickening and stiffening proximal to the coarctation with increasing severity and/or duration of CoA. FSI simulations indicate wall tension in the proximal region increases markedly with coarctation severity. Importantly, even mild CoA induced stimuli for remodeling that exceeds values seen in adulthood if not treated early and using a BPGpp lower than the current clinical threshold. The findings are aligned with observations from other species and provide some guidance for the values of mechanical stimuli that could be used to predict the likelihood of HTN in human patients with CoA.

Collagen-Specific HSP47+ Myofibroblasts and CD163+ Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections.

Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47+ cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections. Because macrophages are also linked to inflammation, we measured CD163+ cells in the same tissues. We observed irregular groups of spindle-shaped HSP47+ and CD163+ cells as well as increased collagen α 1(I) deposition, each proximate to one another in "hot spots" of ≈40% of hearts after SARS-CoV-2 infection (HSP47+ P<0.05 versus nonfibrotics and P<0.001 versus controls). Because HSP47+ cells are consistent with myofibroblasts, subjects with hot spots are termed "profibrotic." The remaining 60% of subjects dying with COVID-19 without hot spots are referred to as "nonfibrotic." No control subject exhibited hot spots. Conclusions Colocalization of myofibroblasts, M2(CD163+) macrophages, and collagen α 1(l) may be the first evidence of a COVID-19-related "profibrotic phenotype" in human hearts in situ. The potential public health and diagnostic implications of these observations require follow-up to further define mechanisms of viral-mediated cardiac fibrosis.

Clinical, Experimental, and Computational Validation of a New Doppler-Based Index for Coarctation Severity Assessment.

BACKGROUND: Long-term morbidity including hypertension often persists in coarctation patients despite current guidelines. Coarctation severity can be invasively assessed via peak-to-peak catheter pressure gradient (PPCG), which is estimated noninvasively via simplified Bernoulli equation and conventionally reported as peak instantaneous Doppler gradient (PIDG). However, underlying simplifications of the equation limit diagnostic accuracy. We studied the diagnostic performance of a new Doppler-based diastolic index called the continuous flow pressure gradient (CFPG) versus conventional indices in assessing coarctation severity. METHODS: In a rabbit model mimicking human aortic coarctation, temporal blood pressure waveforms revealed the diastolic instantaneous pressure gradients and spectral Doppler features impacted by coarctation severity. We therefore hypothesized that CFPG provides superior correlation with coarctation gradients measured invasively. PIDG and CFPG were quantified using color flow echocardiography in humans and rabbits with discrete coarctations. Results were compared with PPCG in rabbits (n = 34) and arm-leg systolic gradients (n = 25) in humans via 1-way analysis of variance, Pearson's correlation, linear regression, and Bland-Altman analysis. RESULTS: A threshold of CFPG ≥ 4.6 mm Hg was identified via the Youden index as representative of PPCG ≥ 20 mm Hg (the current guideline value for coarctation intervention) in rabbits, while a CFPG ≥1.0 mm Hg represented an arm-leg systolic gradient ≥20 mm Hg in humans. Accuracy measures revealed superior correlation of CFPG (R2 > 0.80) and mild receiver operating characteristic improvement (area under the receiver operating characteristic curve, 0.94-0.95) compared with PIDG (R2 < 0.63; area under the receiver operating characteristic curve, 0.89-0.95). Inter-/intraobserver variability tested by intraclass correlation coefficient revealed measurement reliability with differences ≤8.2% and 10.7%, respectively. Computational simulations of anesthetized versus conscious hemodynamics showed parameters were minimally impacted by isoflurane inherent in the data used to derive CFPG. These results confirm the potential diagnostic accuracy of CFPG in echocardiography-based coarctation severity assessment. We are optimistic that CFPG will be useful for translation of results from preclinical studies that revisit current guidelines to limit morbidity in humans with aortic coarctation.

Multiple two-dimensional active shape model framework for right ventricular segmentation.

Segmentation of the right ventricle (RV) in MRI short axis images is very challenging due to its complex shape and various appearance among the different subjects and cross-sections. Active shape models (ASM) have shown potential for segmenting the complex structures, including the RV, through two formulations: two- and three-dimensional modeling with a reported trade-off between accuracy and complexity of each formulation. In this work, we propose a new framework for modeling the RV surface using multiple 2D contours, where information from multiple cross-sectional images are incorporated into the same model. The proposed method was tested using cardiac MRI images from 56 human subjects. Compared to a golden reference of manually delineated RV contours, the proposed method resulted in significantly lower error than (almost one half) that of the conventional 2D ASM especially at the apical slices. The mean absolute distance of the proposed method was 2.9 ± 2 mm while the conventional 2D ASM resulted in an error of 6.6 ± 4.5 mm. In addition, the computation time of the proposed method was 5 s compared to 4 ± 1 min previously reported for the 3D ASM formulation.

Myocardial Contractility Pattern Characterization in Radiation-Induced Cardiotoxicity Using Magnetic Resonance Imaging: A Pilot Study with ContractiX.

Radiation therapy (RT) plays an integral role in treating thoracic cancers, despite the risk of radiation-induced cardiotoxicity. We hypothesize that our newly developed magnetic resonance imaging (MRI)-based contractility index (ContractiX) is a sensitive marker for early detection of RT-induced cardiotoxicity in a preclinical rat model of thoracic cancer RT. Adult salt-sensitive rats received image-guided heart RT and were imaged with MRI at 8 weeks and 10 weeks post-RT or sham. The MRI exam included cine and tagging sequences to measure left-ventricular ejection fraction (LVEF), mass, myocardial strain, and ContractiX. Furthermore, ventricular torsion, diastolic strain rate, and mechanical dyssynchrony were measured. Statistical analyses were performed between the sham, 8 weeks post-RT, and 10 weeks post-RT MRI parameters. The results showed that both LVEF and myocardial mass increased post-RT. Peak systolic strain and ContractiX significantly decreased post-RT, with a more relative reduction in ContractiX compared to strain. ContractiX showed an inverse nonlinear relationship with LVEF and continuously decreased with time post-RT. While early diastolic strain rate and mechanical dyssynchrony significantly changed post-RT, ventricular torsion changes were not significant post-RT. In conclusion, ContractiX measured via non-contrast MRI is a sensitive early marker for the detection of subclinical cardiac dysfunction post-RT, and it is superior to other MRI cardiac measures.

Diastolic Cardiac Function by MRI-Imaging Capabilities and Clinical Applications.

Most cardiac studies focus on evaluating left ventricular (LV) systolic function. However, the assessment of diastolic cardiac function is becoming more appreciated, especially with the increasing prevalence of pathologies associated with diastolic dysfunction like heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction is an indication of abnormal mechanical properties of the myocardium, characterized by slow or delayed myocardial relaxation, abnormal LV distensibility, and/or impaired LV filling. Diastolic dysfunction has been shown to be associated with age and other cardiovascular risk factors such as hypertension and diabetes mellitus. In this context, cardiac magnetic resonance imaging (MRI) has the capability for differentiating between normal and abnormal myocardial relaxation patterns, and therefore offers the prospect of early detection of diastolic dysfunction. Although diastolic cardiac function can be assessed from the ratio between early and atrial filling peaks (E/A ratio), measuring different parameters of heart contractility during diastole allows for evaluating spatial and temporal patterns of cardiac function with the potential for illustrating subtle changes related to age, gender, or other differences among different patient populations. In this article, we review different MRI techniques for evaluating diastolic function along with clinical applications and findings in different heart diseases.

Improving MR Image Quality in Patients with Metallic Implants.

The number of implanted devices such as orthopedic hardware and cardiac implantable devices continues to increase with an increase in the age of the patient population, as well as an increase in the number of indications for specific devices. Many patients with these devices have or will develop clinical conditions that are best depicted at MRI. However, implanted devices containing paramagnetic or ferromagnetic substances can cause significant artifact, which could limit the diagnostic capability of this modality. Performing imaging with MRI when an implant is present may be challenging, and there are numerous techniques the radiologist and technologist can use to help minimize artifacts related to implants. First, knowledge of the presence of an implant before patient arrival is critical to ensure safety of the patient when the device is subjected to a strong magnetic field. Once safety is ensured, the examination should be performed with the MRI system that is expected to provide the best image quality. The selection of the MRI system includes multiple considerations such as the effects of field strength and availability of specific sequences, which can reduce metal artifact. Appropriate patient positioning, attention to MRI parameters (including bandwidth, voxel size, and echo), and appropriate selection of sequences (those with less metal artifact and advanced metal reduction sequences) are critical to improve image quality. Patients with implants can be successfully imaged with MRI with appropriate planning and understanding of how to minimize artifacts. This improves image quality and the diagnostic confidence of the radiologist. ©RSNA, 2021.

Value CMR: Towards a Comprehensive, Rapid, Cost-Effective Cardiovascular Magnetic Resonance Imaging.

Cardiac magnetic resonance imaging (CMR) is considered the gold standard for measuring cardiac function. Further, in a single CMR exam, information about cardiac structure, tissue composition, and blood flow could be obtained. Nevertheless, CMR is underutilized due to long scanning times, the need for multiple breath-holds, use of a contrast agent, and relatively high cost. In this work, we propose a rapid, comprehensive, contrast-free CMR exam that does not require repeated breath-holds, based on recent developments in imaging sequences. Time-consuming conventional sequences have been replaced by advanced sequences in the proposed CMR exam. Specifically, conventional 2D cine and phase-contrast (PC) sequences have been replaced by optimized 3D-cine and 4D-flow sequences, respectively. Furthermore, conventional myocardial tagging has been replaced by fast strain-encoding (SENC) imaging. Finally, T1 and T2 mapping sequences are included in the proposed exam, which allows for myocardial tissue characterization. The proposed rapid exam has been tested in vivo. The proposed exam reduced the scan time from >1 hour with conventional sequences to <20 minutes. Corresponding cardiovascular measurements from the proposed rapid CMR exam showed good agreement with those from conventional sequences and showed that they can differentiate between healthy volunteers and patients. Compared to 2D cine imaging that requires 12-16 separate breath-holds, the implemented 3D-cine sequence allows for whole heart coverage in 1-2 breath-holds. The 4D-flow sequence allows for whole-chest coverage in less than 10 minutes. Finally, SENC imaging reduces scan time to only one slice per heartbeat. In conclusion, the proposed rapid, contrast-free, and comprehensive cardiovascular exam does not require repeated breath-holds or to be supervised by a cardiac imager. These improvements make it tolerable by patients and would help improve cost effectiveness of CMR and increase its adoption in clinical practice.

Cardiac Magnetic Resonance for Early Detection of Radiation Therapy-Induced Cardiotoxicity in a Small Animal Model.

BACKGROUND: Over half of all cancer patients receive radiation therapy (RT). However, radiation exposure to the heart can cause cardiotoxicity. Nevertheless, there is a paucity of data on RT-induced cardiac damage, with limited understanding of safe regional RT doses, early detection, prevention and management. A common initial feature of cardiotoxicity is asymptomatic dysfunction, which if left untreated may progress to heart failure. The current paradigm for cardiotoxicity detection and management relies primarily upon assessment of ejection fraction (EF). However, cardiac injury can occur without a clear change in EF. OBJECTIVES: To identify magnetic resonance imaging (MRI) markers of early RT-induced cardiac dysfunction. METHODS: We investigated the effect of RT on global and regional cardiac function and myocardial T1/T2 values at two timepoints post-RT using cardiac MRI in a rat model of localized cardiac RT. Rats who received image-guided whole-heart radiation of 24Gy were compared to sham-treated rats. RESULTS: The rats maintained normal global cardiac function post-RT. However, a deterioration in strain was particularly notable at 10-weeks post RT, and changes in circumferential strain were larger than changes in radial or longitudinal strain. Compared to sham, circumferential strain changes occurred at the basal, mid-ventricular and apical levels (p<0.05 for all at both 8-weeks and 10-weeks post-RT), most of the radial strain changes occurred at the mid-ventricular (p=0.044 at 8-weeks post-RT) and basal (p=0.018 at 10-weeks post-RT) levels, and most of the longitudinal strain changes occurred at the apical (p=0.002 at 8-weeks post-RT) and basal (p=0.035 at 10-weeks post-RT) levels. Regionally, lateral myocardial segments showed the greatest worsening in strain measurements, and histologic changes supported these findings. Despite worsened myocardial strain post-RT, myocardial tissue displacement measures were maintained, or even increased. T1/T2 measurements showed small non-significant changes post-RT compared to values in non-irradiated rats. CONCLUSIONS: Our findings suggest MRI regional myocardial strain is a sensitive imaging biomarker for detecting RT-induced subclinical cardiac dysfunction prior to compromise of global cardiac function.

Cardiac functional magnetic resonance imaging at 7T: Image quality optimization and ultra-high field capabilities.

BACKGROUND: 7T cardiac magnetic resonance imaging (MRI) introduces several advantages, as well as some limitations, compared to lower-field imaging. The capabilities of ultra-high field (UHF) MRI have not been fully exploited in cardiac functional imaging. AIM: To optimize 7T cardiac MRI functional imaging without the need for conducting B1 shimming or subject-specific tuning, which improves scan efficiency. In this study, we provide results from phantom and in vivo scans using a multi-channel transceiver modular coil. METHODS: We investigated the effects of adding a dielectric pad at different locations next to the imaged region of interest on improving image quality in subjects with different body habitus. We also investigated the effects of adjusting the imaging flip angle in cine and tagging sequences on improving image quality, B1 field homogeneity, signal-to-noise ratio (SNR), blood-myocardium contrast-to-noise ratio (CNR), and tagging persistence throughout the cardiac cycle. RESULTS: The results showed the capability of achieving improved image quality with high spatial resolution (0.75 mm × 0.75 mm × 2 mm), high temporal resolution (20 ms), and increased tagging persistence (for up to 1200 ms cardiac cycle duration) at 7T cardiac MRI after adjusting scan set-up and imaging parameters. Adjusting the imaging flip angle was essential for achieving optimal SNR and myocardium-to-blood CNR. Placing a dielectric pad at the anterior left position of the chest resulted in improved B1 homogeneity compared to other positions, especially in subjects with small chest size. CONCLUSION: Improved regional and global cardiac functional imaging can be achieved at 7T MRI through simple scan set-up adjustment and imaging parameter optimization, which would allow for more streamlined and efficient UHF cardiac MRI.

A Pilot Study of Cardiac MRI in Breast Cancer Survivors After Cardiotoxic Chemotherapy and Three-Dimensional Conformal Radiotherapy.

PURPOSE/OBJECTIVES: Node-positive breast cancer patients often receive chemotherapy and regional nodal irradiation. The cardiotoxic effects of these treatments, however, may offset some of the survival benefit. Cardiac magnetic resonance (CMR) is an emerging modality to assess cardiac injury. This is a pilot trial assessing cardiac damage using CMR in patients who received anthracycline-based chemotherapy and three-dimensional conformal radiotherapy (3DCRT) regional nodal irradiation using heart constraints. MATERIALS AND METHODS: Node-positive breast cancer patients (2000-2008) treated with anthracycline-based chemotherapy and 3DCRT regional nodal irradiation (including the internal mammary chain nodes) with heart ventricular constraints (V25 < 10%) were invited to participate. Cardiac tissues were contoured and analyzed separately for whole heart (pericardium) and for combined ventricles and left atrium (myocardium). CMR obtained ventricular function/dimensions, late gadolinium enhancement (LGE), global longitudinal strain (GLS), and extracellular volume fraction (ECV) as measures of cardiac injury and/or early fibrosis. CMR parameters were correlated with dose-volume constraints using Spearman correlations. RESULTS: Fifteen left-sided and five right-sided patients underwent CMR. Median diagnosis age was 50 (32-77). No patients had baseline cardiac disease before regional nodal irradiation. Median time after 3DCRT was 8.3 years (5.2-14.4). Median left-sided mean heart dose (MHD) was 4.8 Gy (1.1-11.2) and V25 was 5.7% (0-12%). Median left ventricular ejection fraction (LVEF) was 63%. No abnormal LGE was observed. No correlations were seen between whole heart doses and LVEF, LV mass, GLS, or LV dimensions. Increasing ECV did not correlate with increased heart or ventricular doses. However, correlations between higher LV mass and ventricular mean dose, V10, and V25 were seen. CONCLUSION: At a median follow-up of 8.3 years, this cohort of node-positive breast cancer patients who received anthracycline-based chemotherapy and regional nodal irradiation had no clinically abnormal CMR findings. However, correlations between ventricular mean dose, V10, and V25 and LV mass were seen. Larger corroborating studies that include advanced techniques for measuring regional heart mechanics are warranted.

Optimized cardiac functional MRI of small-animal models of cancer radiation therapy.

Cardiac MRI of small animal models of cancer radiation therapy (RT) is a valuable tool for studying the effect of RT on the heart. However, standard cardiac MRI exams require long scanning times, which is challenging for sick animals that may not survive extended periods of imaging under anesthesia. The purpose of this study is to develop an optimized, fast MRI exam for comprehensive cardiac functional imaging of small-animal models of cancer RT. Ten adult female rats (2 non-irradiated and 8 irradiated) were scanned using the developed exam. Optimal imaging parameters were determined, which minimized scanning time while ensuring measurement accuracy and avoiding imaging artifacts. This optimized, fast MRI exam lasted for 30 min, which was tolerated by all animals. EF was normal in all imaged rats, although it was significantly increased in the irradiated rats, which also showed ventricular hypertrophy. However, myocardial strain was significantly reduced in the irradiated rats. In conclusion, a fast MRI exam has been developed for comprehensive cardiac functional imaging of rats in 30 min, with optimized imaging parameters to ensure accurate measurements and tolerance by irradiated rats. The generated strain measurements provide an early marker of regional cardiac dysfunction before global function is affected.

Cardiac MRI for Patients With Cardiac Implantable Electronic Devices.

OBJECTIVE. Patients with cardiac implantable electronic devices (CIEDs) require cardiac MRI (CMRI) for a variety of reasons. The purpose of this study is to review and evaluate the value and safety of CMRI for patients with in situ CIEDs. CONCLUSION. Late gadolinium enhancement CMRI is the reference standard for assessing myocardial viability in patients with ventricular tachycardia before ablation of arrhythmogenic substrates. The use of late gadolinium enhancement CMRI for patients with CIEDs is safe as long as an imaging protocol is in place and precaution measures are taken.