Harsh K. Agarwal

Regional coronary endothelial function is closely related to local early coronary atherosclerosis in patients with mild coronary artery disease: pilot study.

Background— Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness. Methods and Results— Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (−2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=−0.73, P=0.0008). Conclusions— There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.

Assessment of distribution and evolution of Mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance

BackgroundWe sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality.MethodsCine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice.ResultsMean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p < 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s).ConclusionsMechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct.

Right Coronary MR Angiography at 7 T: A Direct Quantitative and Qualitative Comparison with 3 T in Young Healthy Volunteers

PURPOSE To objectively compare quantitative parameters related to image quality attained at coronary magnetic resonance (MR) angiography of the right coronary artery (RCA) performed at 7 T and 3 T. MATERIALS AND METHODS Institutional review board approval was obtained, and volunteers provided signed informed consent. Ten healthy adult volunteers (mean age ± standard deviation, 25 years ± 4; seven men, three women) underwent navigator-gated three-dimensional MR angiography of the RCA at 7 T and 3 T. For 7 T, a custom-built quadrature radiofrequency transmit-receive surface coil was used. At 3 T, a commercial body radiofrequency transmit coil and a cardiac coil array for signal reception were used. Segmented k-space gradient-echo imaging with spectrally selective adiabatic fat suppression was performed, and imaging parameters were similar at both field strengths. Contrast-to-noise ratio between blood and epicardial fat; signal-to-noise ratio of the blood pool; RCA vessel sharpness, diameter, and length; and navigator efficiency were quantified at both field strengths and compared by using a Mann-Whitney U test. RESULTS The contrast-to-noise ratio between blood and epicardial fat was significantly improved at 7 T when compared with that at 3 T (87 ± 34 versus 52 ± 13; P = .01). Signal-to-noise ratio of the blood pool was increased at 7 T (109 ± 47 versus 67 ± 19; P = .02). Vessel sharpness obtained at 7 T was also higher (58% ± 9 versus 50% ± 5; P = .04). At the same time, RCA vessel diameter and length and navigator efficiency showed no significant field strength-dependent difference. CONCLUSION In our quantitative and qualitative study comparing in vivo human imaging of the RCA at 7 T and 3 T in young healthy volunteers, parameters related to image quality attained at 7 T equal or surpass those from 3 T.

A Phase I Dosing Study of Ferumoxytol for MR Lymphography at 3 T in Patients With Prostate Cancer

OBJECTIVE The objective of our study was to determine the optimal dose of ferumoxytol for performing MR lymphography (MRL) at 3 T in patients with prostate cancer. SUBJECTS AND METHODS This phase I trial enrolled patients undergoing radical prostatectomy (RP) with bilateral pelvic lymph node dissection (PLND). Three groups of five patients each (total of 15 patients) received IV ferumoxytol before RP with bilateral PLND at each of the following doses of iron: 4, 6, and 7.5 mg Fe/kg. Patients underwent abdominopelvic MRI at 3 T before and 24 hours after ferumoxytol injection using T2- and T2*-weighted sequences. Normalized signal intensity (SI) and normalized SD changes from baseline to 24 hours after injection within visible lymph nodes were calculated for each dose level. Linear mixed effects models were used to estimate the effects of dose on the percentage SI change and log-transformed SD change within visible lymph nodes to determine the optimal dose of ferumoxytol for achieving uniform low SI in normal nodes. RESULTS One patient who was excluded from the study group had a mild allergic reaction requiring treatment after approximately 2.5 mg Fe/kg ferumoxytol injection whereupon the injection was interrupted. The 15 study group patients tolerated ferumoxytol at all dose levels. The mean percentage SI change in 13 patients with no evidence of lymph metastasis was -36.4%, -45.4%, and -65.1% for 4, 6, and 7.5 mg Fe/kg doses, respectively (p = 0.041). CONCLUSION A dose level of 7.5 mg Fe/kg ferumoxytol was safe and effective in deenhancing benign lymph nodes. This dose therefore can be the starting point for future phase II studies regarding the efficacy of ferumoxytol for MRL.

Practical signal-to-noise ratio quantification for sensitivity encoding: Application to coronary MR angiography

To develop and evaluate a practical method for the quantification of signal‐to‐noise ratio (SNR) on coronary MR angiograms (MRA) acquired with parallel imaging.

Functional and molecular imaging of localized and recurrent prostate cancer

Prostate cancer is the most common malignancy among American men. Imaging of localized and recurrent prostate cancer is challenging since conventional imaging techniques are limited. New imaging techniques such as multiparametric MRI and PET with targeted tracers have been investigated extensively in the last decade. As a result, the role of novel imaging techniques for the detection of localized and recurrent prostate cancer has recently expanded. In this review, novel functional and molecular imaging techniques used in the management of localized and recurrent prostate cancer are discussed.

Magnetic Resonance Sentinel Lymph Node Imaging of the Prostate with Gadofosveset Trisodium–Albumin: Preliminary Results in a Canine Model

RATIONALE AND OBJECTIVES To determine if intraprostatic injection of gadofosveset trisodium mixed with human serum albumin (HSA) can identify sentinel lymph nodes (LNs) draining the prostate on magnetic resonance imaging (MRI) in a canine model. MATERIALS AND METHODS Three male canines weighing between 25.7 and 41.3 kg were anesthetized, placed in a 3-T MRI, and a needle was placed transrectally into one side of the prostate using a commercially available intrarectal needle guide. Gadofosveset trisodium premixed with 10% HSA was then administered at doses ranging from 0.1 to 2.5 mL. T1W MRI was performed immediately after injection, and two readers evaluated images for visualization of LNs draining the prostate. RESULTS Intraprostatic injection of 0.2 mL gadofosveset trisodium premixed with HSA identified the draining periprostatic LNs in all cases. Delayed images demonstrated upper echelon nodes in the pelvis and the abdomen. Higher volume injections resulted in excessive periprostatic extravasation, whereas lower volume injections resulted in suboptimal visualization of LNs. CONCLUSIONS We demonstrate that gadofosveset trisodium (premixed with 10% HSA) injected intraprostatically at 0.2 mL visualized LNs draining the prostate. This approach can be readily adapted for clinical applications such as sentinel LN imaging in prostate cancer patients before surgery.

Three-dimensional regional strain analysis in porcine myocardial infarction: A 3T magnetic resonance tagging study

BackgroundPrevious studies of mechanical strain anomalies in myocardial infarction (MI) have been largely limited to analysis of one-dimensional (1D) and two-dimensional (2D) strain parameters. Advances in cardiovascular magnetic resonance (CMR) methods now permit a complete three-dimensional (3D) interrogation of myocardial regional strain. The aim of this study was to investigate the incremental value of CMR-based 3D strain and to test the hypothesis that 3D strain is superior to 1D or 2D strain analysis in the assessment of viability using a porcine model of infarction.MethodsInfarction was induced surgically in 20 farm pigs. Cine, late gadolinium enhancement, and CMR tagging images were acquired at 11 days before (baseline), and 11 days (early) and 1 month (late) after induction of infarct. Harmonic phase analysis was performed to measure circumferential, longitudinal, and radial strains in myocardial segments, which were defined based on the transmurality of delayed enhancement. Univariate, bivariate, and multivariate logistic regression models of strain parameters were created and analyzed to compare the overall diagnostic accuracy of 3D strain analysis with 1D and 2D analyses in identifying the infarct and its adjacent regions from healthy myocardium.Results3D strain differed significantly in infarct, adjacent, and remote segments (p < 0.05) at early and late post-MI. In univariate, bivariate, and multivariate analyses, circumferential, longitudinal, and radial strains were significant factors (p < 0.001) in differentiation of infarct and adjacent segments from baseline values. In identification of adjacent segments, receiver operating characteristic analysis using the 3D strain multivariate model demonstrated a significant improvement (p < 0.01) in overall diagnostic accuracy in comparison with 2D (circumferential and radial) and 1D (circumferential) models (3D: 96%, 2D: 81%, and 1D: 71%). A similar trend was observed in identification of infarct segments.ConclusionsCumulative 3D strain information accurately identifies infarcts and their neighboring regions from healthy myocardium. The 3D interrogation of myocardial contractility provides incremental diagnostic accuracy in delineating the dysfunctional and nonviable myocardium in comparison with 1D or 2D quantification of strain. The infarct neighboring regions are the major beneficiaries of the 3D assessment of regional strain.

Total removal of unwanted harmonic peaks (TruHARP) MRI for single breath-hold high-resolution myocardial motion and strain quantification

Current MRI methods for myocardial motion and strain quantification have limited resolution because of Fourier space spectral peak interference. Methods have been proposed to remove this interference in order to improve resolution; however, these methods are clinically impractical due to the prolonged imaging times. In this paper, we propose total removal of unwanted harmonic peaks (TruHARP); a myocardial motion and strain quantification methodology that uses a novel single breath‐hold MR image acquisition protocol. In post‐processing, TruHARP separates the spectral peaks in the acquired images, enabling high‐resolution motion and strain quantification. The impact of high resolution on calculated circumferential and radial strains is studied using realistic Monte Carlo simulations, and the improvement in strain maps is demonstrated in six human subjects. Magn Reson Med, 2010.

Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone

To retrospectively determine the optimal b‐value(s) of diffusion‐weighted imaging (DWI) associated with intermediate–high risk cancer in the peripheral zone (PZ) of the prostate.