Jeffrey A. Stainsby

Occult Cardiotoxicity in Childhood Cancer Survivors Exposed to Anthracycline Therapy

Background—More than 50% of >270 000 childhood cancer survivors in the United States have been treated with anthracyclines and are therefore at risk of developing cardiotoxicity. Cardiac magnetic resonance (CMR) has demonstrated utility to detect diffuse interstitial fibrosis and changes in regional myocardial function. We hypothesized that CMR would identify occult cardiotoxicity characterized by structural and functional myocardial abnormalities in a cohort of asymptomatic pediatric cancer survivors with normal global systolic function. Methods and Results—Forty-six long-term childhood cancer survivors with a cumulative anthracycline dose ≥200 mg/m2 and normal systolic function were studied 2.5 to 26.9 years after anthracycline exposure. Subjects underwent transthoracic echocardiography, CMR with routine cine acquisition, tissue characterization, and left ventricular strain analysis using a modified 16-segment model. Extracellular volume was measured in 27 subjects, all of whom were late gadolinium enhancement negative. End-systolic fiber stress was elevated in 45 of 46 subjects. Low average circumferential strain magnitude (&egr;cc) −14.9±1.4; P<0.001, longitudinal strain magnitude (&egr;ll) −13.5±1.9; P<0.001, and regional peak circumferential strain were seen in multiple myocardial segments, despite normal global systolic function by transthoracic echocardiography and CMR. The mean T1 values of the myocardium were significantly lower than that of control subjects at 20 minutes (458±69 versus 487±44 milliseconds; P=0.01). Higher mean extracellular volume was observed in female subjects (0.34 versus 0.22; P=0.01). Conclusions—Asymptomatic postchemotherapy pediatric patients have abnormal myocardial characteristics and strain parameters by CMR despite normal global cardiac function by standard transthoracic echocardiography and CMR measures.

Inversion‐recovery‐prepared SSFP for cardiac‐phase‐resolved delayed‐enhancement MRI

Delayed‐enhancement magnetic resonance imaging (DE‐MRI) can be used to visualize myocardial infarction (MI). DE‐MRI is conventionally acquired with an inversion‐recovery gradient‐echo (IR‐GRE) pulse sequence that yields a single bright‐blood image. IR‐GRE imaging requires an accurate estimate of the inversion time (TI) to null the signal from the myocardium, and a separate cine acquisition is required to visualize myocardial wall motion. Simulations were performed to examine the effects of a steady‐state free precession (SSFP) readout after an inversion pulse in the setting of DE‐MRI. Using these simulations, a segmented IR‐SSFP sequence was optimized for infarct visualization. This sequence yields both viability and wall motion images over the cardiac cycle in a single breath‐hold. Viability images at multiple effective TIs are produced, providing a range of image contrasts. In a study of 11 patients, IR‐SSFP yielded infarct sizes and left ventricular ejection fractions (LVEFs) similar to those obtained by IR‐GRE and standard SSFP, respectively. IR‐SSFP images yielded improved visualization of the infarct‐blood border because of the simultaneous nulling of healthy myocardium and blood. T  1* recovery curves were extracted from IR‐SSFP images and showed excellent qualitative agreement with theoretical simulations. Magn Reson Med 58:365–372, 2007.

Development of a geometrically accurate imaging protocol at 3 Tesla MRI for stereotactic radiosurgery treatment planning.

The purpose of this study is to develop a geometrically accurate imaging protocol at 3 T magnetic resonance imaging (MRI) for stereotactic radiosurgery (SRS) treatment planning. In order to achieve this purpose, a methodology is developed to investigate the geometric accuracy and stability of 3 T MRI for SRS in phantom and patient evaluations. Forty patients were enrolled on a prospective clinical trial. After frame placement prior to SRS, each patient underwent 3 T MRI after 1.5 T MRI and CT. MR imaging protocols included a T1-weighted gradient echo sequence and a T2-weighted spin echo sequence. Phantom imaging was performed on 3 T prior to patient imaging using the same set-up and imaging protocols. Geometric accuracy in patients and phantoms yielded comparable results for external fiducial reference deviations and internal landmarks between 3 T and 1.5 T MRI (mean ≤ 0.6 mm; standard deviation ≤ 0.3 mm). Mean stereotactic reference deviations between phantoms and patients correlated well (T1: R = 0.79; T2: R = 0.84). Statistical process control analysis on phantom QA data demonstrated the stability of our SRS imaging protocols, where the geometric accuracy of the 3 T SRS imaging protocol is operating within the appropriate tolerance. Our data provide evidence supporting the spatial validity of 3 T MRI for targeting SRS under imaging conditions investigated. We have developed a systematic approach to achieve confidence on the geometric integrity of a given imaging system/technique for clinical integration in SRS application.

Flexible cardiac T1 mapping using a modified look–locker acquisition with saturation recovery

A modified Look–Locker acquisition using saturation recovery (MLLSR) for breath‐held myocardial T1 mapping is presented. Despite its reduced dynamic range, saturation recovery enables substantially higher imaging efficiency than conventional inversion recovery T1 mapping because it does not require time for magnetization to relax to equilibrium. Therefore, MLLSR enables segmented readouts, shorter data acquisition windows, and shorter breath holds compared with inversion recovery. T1 measurements in phantoms using MLLSR showed a high correlation with conventional single‐point inversion recovery spin echo. In vivo T1 measurements from normal and infarcted myocardium in 41 volunteers and patients were consistent with previously reported values. Twenty subjects were also scanned with MLLSR using an accelerated sampling scheme that required half the scan time (eight vs. 16 heartbeats) but yielded equivalent results. The flexibility afforded by the improved imaging efficiency of MLLSR allows the acquisition to be tailored to particular clinical needs and to individual patients breath‐holding abilities. Magn Reson Med, 2012.

Vascular Steal Explains Early Paradoxical Blood Oxygen Level-Dependent Cerebrovascular Response in Brain Regions with Delayed Arterial Transit Times

Introduction: Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) during manipulation of inhaled carbon dioxide (CO2) can be used to measure cerebrovascular reactivity (CVR) and map regions of exhausted cerebrovascular reserve. These regions exhibit a reduced or negative BOLD response to inhaled CO2. In this study, we sought to clarify the mechanism behind the negative BOLD response by investigating its time delay (TD). Dynamic susceptibility contrast (DSC) MRI with the injection of a contrast agent was used as the gold standard in order to provide measurement of the blood arrival time to which CVR TD could be compared. We hypothesize that if negative BOLD responses are the result of a steal phenomenon, they should be synchronized with positive BOLD responses from healthy brain tissue, even though the blood arrival time would be delayed. Methods: On a 3-tesla MRI system, BOLD CVR and DSC images were collected in a group of 19 patients with steno-occlusive cerebrovascular disease. For each patient, we generated a CVR magnitude map by regressing the BOLD signal with the end-tidal partial pressure of CO2 (PETCO2), and a CVR TD map by extracting the time of maximum cross-correlation between the BOLD signal and PETCO2. In addition, a blood arrival time map was generated by fitting the DSC signal with a gamma variate function. ROI masks corresponding to varying degrees of reactivity were constructed. Within these masks, the mean CVR magnitude, CVR TD and DSC blood arrival time were extracted and averaged over the 19 patients. CVR magnitude and CVR TD were then plotted against DSC blood arrival time. Results: The results show that CVR magnitude is highly correlated to DSC blood arrival time. As expected, the most compromised tissues with the longest blood arrival time have the lowest (most negative) CVR magnitude. However, CVR TD shows a noncontinuous relationship with DSC blood arrival time. CVR TD is well correlated to DSC blood arrival time (p < 0.0001) for tissue of positive reactivity, but fails to maintain this trend for tissue of negative reactivity. Regions with negative reactivity have similar CVR TD than healthy regions. Conclusion: These results support the hypothesis that negative reactivity is the result of a steal phenomenon, lowering the BOLD signal as soon as healthier parts of the brain start to react and augment their blood flow. BOLD CVR MRI is capable of identifying this steal distribution, which has particular diagnostic significance as it represents an actual reduction in flow to already compromised tissue.

CLINICAL EVALUATION OF STEREOTACTIC TARGET LOCALIZATION USING 3-TESLA MRI FOR RADIOSURGERY PLANNING

PURPOSE Increasing the magnetic resonance imaging (MRI) field strength can improve image resolution and quality, but concerns remain regarding the influence on geometric fidelity. The objectives of the present study were to spatially investigate the effect of 3-Tesla (3T) MRI on clinical target localization for stereotactic radiosurgery. METHODS AND MATERIALS A total of 39 patients were enrolled in a research ethics board-approved prospective clinical trial. Imaging (1.5T and 3T MRI and computed tomography) was performed after stereotactic frame placement. Stereotactic target localization at 1.5T vs. 3T was retrospectively analyzed in a representative cohort of patients with tumor (n = 4) and functional (n = 5) radiosurgical targets. The spatial congruency of the tumor gross target volumes was determined by the mean discrepancy between the average gross target volume surfaces at 1.5T and 3T. Reproducibility was assessed by the displacement from an averaged surface and volume congruency. Spatial congruency and the reproducibility of functional radiosurgical targets was determined by comparing the mean and standard deviation of the isocenter coordinates. RESULTS Overall, the mean absolute discrepancy across all patients was 0.67 mm (95% confidence interval, 0.51-0.83), significantly <1 mm (p < .010). No differences were found in the overall interuser target volume congruence (mean, 84% for 1.5T vs. 84% for 3T, p > .4), and the gross target volume surface mean displacements were similar within and between users. The overall average isocenter coordinate discrepancy for the functional targets at 1.5T and 3T was 0.33 mm (95% confidence interval, 0.20-0.48), with no patient-specific differences between the mean values (p >.2) or standard deviations (p >.1). CONCLUSION Our results have provided clinically relevant evidence supporting the spatial validity of 3T MRI for use in stereotactic radiosurgery under the imaging conditions used.

Free-breathing, nongated real-time delayed enhancement MRI of myocardial infarcts: A comparison with conventional delayed enhancement

To compare a free‐breathing, nongated, and black‐blood real‐time delayed enhancement (RT‐DE) sequence to the conventional inversion recovery gradient echo (IR‐GRE) sequence for delayed enhancement MRI.

Noninvasive quantitative measurement of myocardial and whole-body oxygen consumption using MRI : initial results

The purpose of this study was to investigate the feasibility of a noninvasive approach that combines magnetic resonance imaging (MRI) oximetry and flow measurement to obtain the oxygen consumption in the myocardium and in the whole body. Thirteen healthy male volunteers [mean (+/-S.D.) age: 35+/-7 years] underwent this MR study, which included myocardial oxygen consumption (MVO(2)) measurements in 11 subjects and whole-body oxygen consumption (VO(2)) measurements in 8 subjects. In six subjects, both measurements were obtained. Five subjects had repeated MRI measurements of global MVO(2) in order to verify the reproducibility of this approach. The protocol included in vitro blood sample T(2)-%O(2) calibration, coronary sinus (CS) and main pulmonary artery (MPA) T(2) and phase contrast flow measurement and left ventricular (LV) mass calculation. Based on Ficks law, a global measurement of LV MVO(2) and whole-body VO(2) using MRI was feasible. The MVO(2) values were 11+/-3 ml/min per 100 g LV mass. For repeated measurements, differences in MVO(2) of 1 ml/min per 100 g LV mass appear detectable. The whole-body VO(2) values were 3.8+/-0.8 ml/min/kg body weight. MRI techniques that combine CS and MPA T(2), flow and LV mass measurements to quantify MVO(2) and whole-body VO(2) noninvasively in healthy subjects appear feasible, based on their correspondence to previously published work.

Practical aspects of MR imaging in the presence of conductive guide wires.

Various aspects of RF-induced heating of guide wires during their MRI guidance have been investigated in the past. However, the previous works focused on inducing tip heating in either fully immersed or tip-immersed (and otherwise free) wires of impractical lengths in small phantoms. This study simulates real clinical conditions using a product guide wire and a same-length conductive wire partially inserted into a torso-size phantom filled with saline solution. The purpose was to identify potential safety concerns relevant to real clinical applications, as opposed to identifying the worst-case heating scenario. Significant heating occurred at the insertion point, independent of tip heating, with a strong correlation with excitation frequency-dependent imaging parameters. Heat transfer through the wire was also demonstrated to be a safety concern. From these experiments, we have been able to demonstrate additional impacting factors that increase the complexity of safety considerations for the use of conductive guide wires during MR imaging. Safety under a particular set of conditions does not imply safety in all possible conditions that can be encountered during real MRI-guided interventions.

Visualization of ablation lesions by dynamic contrast-enhanced (DynCE) MRI

Introduction Intra-operative lesion visualization is important during ablative cardiac procedures whose success depends on the contiguity and transmurality of the ablation lesions. The usefulness of contrast kinetics analysis for thermal lesion visualization has been already demonstrated [1,2]. However, the method relied on lengthy image acquisition and model-based curve fitting of complete data sets. Delayed enhancement (DE) methods [3-5] required lengthy scan and waiting (after contrast agent, CA, injection) times. Non-enhanced visualization [6] delivered lower lesion-tobackground contrasts. We report a novel method for analyzing MRI-apparent contrast uptake dynamics, which allows robust and quick visualization of RF lesions.