Mark L. Schiebler

Imaging of Lung Function using Hyperpolarized Helium-3 Magnetic Resonance Imaging: Review of Current and Emerging Translational Methods and Applications

During the past several years there has been extensive development and application of hyperpolarized helium‐3 (HP 3He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation‐induced lung injury, and transplantation. This review focuses on the state‐of‐the‐art of HP 3He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine. Particular attention is given to functional imaging approaches related to ventilation and diffusion‐weighted imaging with applications in chronic obstructive pulmonary disease, cystic fibrosis, asthma, and radiation‐induced lung injury. The strengths and challenges of the application of 3He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques. J. Magn. Reson. Imaging 2010;32:1398–1408.

Optimized 3D ultrashort echo time pulmonary MRI

To optimize 3D radial ultrashort echo time MRI for high resolution whole‐lung imaging.

Noninvasive determination of coronary artery bypass graft patency by cine magnetic resonance imaging.

Cine magnetic resonance imaging (MRI) is a gradient-recalled, retrospectively gated, fast-scan technique that depicts laminar flowing blood as bright signal and has been proposed as a useful method for determination of coronary artery bypass graft (CABG) patency. Therefore, we performed a blinded prospective study to assess the value of cine MRI determination of CABG patency in 20 patients with 45 CABG proximal anastomoses who were undergoing repeat angiography. Ten normal subjects served as controls to define normal intrathoracic vascular patterns. There were 21 left anterior descending (LAD) grafts, of which four were left internal mammary (LIMA), 12 left circumflex (Cx), and 12 right coronary (RCA) grafts. After localizing spin-echo coronal images were obtained, multiple axial multislice interleaved cine MRI acquisitions, each consisting of two to four 5-10-mm-thick slices at eight to 24 frames per cardiac cycle, were obtained from the superior main pulmonary artery to the inferior left ventricle. Each acquisition took 5-8 minutes with a subsequent 5-10 minutes of computer image reconstruction. Total study time per patient was 50-75 minutes. Known to cine MRI interpreters were the original surgical CABG insertions but not the angiographic findings. A graft was called patent if a bright graft flow signal, not corresponding to a normal vessel, was identified on multiple frames at multiple levels abutting the great vessels or epicardial surface of the heart. Angiographically, there were 33 patent grafts, of which 29 were identified as patent by cine MRI (sensitivity, 88%).(ABSTRACT TRUNCATED AT 250 WORDS)

4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot

BackgroundTo assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR).MethodsCMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fishers exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test.Results4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PAs. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant.ConclusionsWhole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics.

Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations

Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation‐prone asthma (EPA) remain incompletely defined. Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA. Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)‐3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (≥3). Replication of a multivariable model was performed with data from the SARP‐1 + 2 cohort. Measurements and Main Results: Of 709 subjects in the SARP‐3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP‐3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP‐3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2‐2.1] for every log unit of eosinophils, 1.3 [1.1‐1.4] for every 10 body mass index units, and 1.2 [1.1‐1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4‐2.1] and 1.6 [1.3‐2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP‐1 + 2 multivariable model. Conclusions: EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).

In vivo and ex vivo magnetic resonance imaging evaluation of early disc degeneration with histopathologic correlation

The in vivo and ex vivo microanatomic appearance of early disc degeneration were identified by magnetic resonance imaging and correlated with their respective histopathologic findings. Five cadaver spines (18 discs) and 25 patient studies (122 discs) all imaged at 1.5 Tesla were studied. Two signs of early degenerative disc disease were found: infolding and the central dot. Infolding of the central fibers of the outer annulus coalesced into a central dot of low signal intensity that was seen on both the ex vivo and in vivo images. Infolding was seen 29 of 122 times, and the central dot was observed 15 to 122 times on the in vivo images. A later form of degenerative disc disease was identified as a separation of the nucleus pulposus from the hyaline cartilage end-plate. This separation was seen as a linear area of either low or high signal intensity on the ex vivo images but only as a band of high signal intensity on the in vivo spin-echo 2,500-msec/80-msec images. Only 7 of 122 in vivo discs showed this separation. Internal herniation of nucleus pulposus into the outer annulus was seen only on the ex vivo images. Early degenerative disc disease may exist before there is loss of disc height or signal intensity on the long time-to-repetition (TR)/time-to-echo (TE) magnetic resonance images.

Evaluation of mitral regurgitation by cine magnetic resonance imaging

We used cine magnetic resonance imaging (MRI) to assess mitral regurgitation (MR) in 40 patients with coronary and/or valvular disease and 10 normal subjects and compared results to pulsed (n = 30) or color flow Doppler mapping (n = 20). Mitral regurgitation produced a dynamic signal void in the left atrium in systole in 15 of 16 patients with MR by pulsed Doppler and in an additional 15 of 16 patients whose MR was demonstrated by color flow Doppler. There were no false positives (sensitivity 94%, specificity 100% for both). The ratio of single-plane, maximal jet area to left atrial area was used to grade MR severity with mild defined as less than 20%, moderate between 20 and 40% and severe greater than 40%. Cine MRI classification was identical to pulsed Doppler echocardiography in 26 of 30 patients and to color flow Doppler in 16 of 20 patients with no differences of greater than 1 grade. Cine MRI consistently depicted smaller flow disturbances than pulsed Doppler (slope = 0.65) or color flow Doppler (slope = 0.60). Nonetheless, the cine MRI area ratio correlated well with pulsed Doppler (r = 0.78) and with color flow Doppler (r = 0.74). Thus, planar analysis of cine MRI in patients with MR of varying severity gave results that were similar to Doppler echocardiography. At present, for routine clinical assessment of MR, the benefits of cine MRI may be limited to patients in whom transthoracic Doppler echocardiography is not adequate.

Correlation of Cine Mr Imaging with Two-dimensional Pulsed Doppler Echocardiography in Valvular Insufficiency

Eight adults with known valvular insufficiency were studied with cine magnetic resonance (MR) imaging. Our cine MR uses cardiac synchronization of a rapid small flip angle pulse sequence on a 1.5 T MR system. Eleven regurgitant lesions (including aortic, mitral, and tricuspid valves) were imaged with both cine MR and two-dimensional pulsed Doppler echocardiography (2-DPDE). In each case of significant regurgitation the jet of valvular insufficiency was easily seen as a discrete area of low signal with cine MR. Not only was the regurgitant jet identified but also its relative severity agreed well with the 2-DPDE results. In two patients the regurgitant lesions were identified on cine MR prior to 2-DPDE. In addition to the regurgitant jet, chamber enlargement and wall thickening were also well demonstrated. Cine MR is a promising modality for both the detection and semiquantification of valvular insufficiency.

Noninvasive assessment of transstenotic pressure gradients in porcine renal artery stenoses by using vastly undersampled phase-contrast MR angiography.

PURPOSE To compare noninvasive transstenotic pressure gradient (TSPG) measurements derived from high-spatial- and temporal-resolution four-dimensional magnetic resonance (MR) flow measurements with invasive measurements obtained from endovascular pressure wires with digital subtraction angiographic guidance. MATERIALS AND METHODS After Animal Care and Use Committee approval, bilateral renal artery stenosis (RAS) was created surgically in 12 swine. Respiratory-gated phase-contrast vastly undersampled isotropic projection (VIPR) MR angiography of the renal arteries was performed with a 1.5-T clinical MR system (repetition time, 11.4 msec; echo time [first echo], 3.7 msec; 18,000 projection angles; imaging volume, 260 × 260 × 200 mm; acquired isotropic spatial resolution, 1.0 × 1.0 × 1.0 mm; velocity encoding, 150 cm/sec). Velocities measured with phase-contrast VIPR were used to calculate TSPGs by using Navier-Stokes equations. These were compared with endovascular pressure measurements (mean and peak) performed by using fluoroscopic guidance with regression analysis. RESULTS In 19 renal arteries with an average stenosis of 62% (range, 0%-87%), there was excellent correlation between the noninvasive TSPG measurement with phase-contrast VIPR and invasive TSPG measurement for mean TSPG (R² = 95.4%) and strong correlation between noninvasive TSPG and invasive TSPG for the peak TSPG measures (R² = 82.6%). The phase-contrast VIPR-derived TSPG measures were slightly lower than the endovascular measurements. In four arteries with severe stenoses and one occlusion (mean, 86%; range, 75%-100%), the residual lumen within the stenosis was too small to determine TSPG with phase-contrast VIPR. CONCLUSION The unenhanced MR angiographic technique with phase-contrast VIPR allows for accurate noninvasive assessment of hemodynamic significance in a porcine model of RAS with highly accurate TSPG measurements.

Effectiveness of MR angiography for the primary diagnosis of acute pulmonary embolism: clinical outcomes at 3 months and 1 year.

To determine the effectiveness of MR angiography for pulmonary embolism (MRA‐PE) in symptomatic patients.