Low drive field amplitude for improved image resolution in magnetic particle imaging.

PURPOSE: Magnetic particle imaging (MPI) is a new imaging technology that directly detects superparamagnetic iron oxide nanoparticles. The technique has potential medical applications in angiography, cell tracking, and cancer detection. In this paper, the authors explore how nanoparticle relaxation affects image resolution. Historically, researchers have analyzed nanoparticle behavior by studying the time constant of the nanoparticle physical rotation. In contrast, in this paper, the authors focus instead on how the time constant of nanoparticle rotation affects the final image resolution, and this reveals nonobvious conclusions for tailoring MPI imaging parameters for optimal spatial resolution. METHODS: The authors first extend x-space systems theory to include nanoparticle relaxation. The authors then measure the spatial resolution and relative signal levels in an MPI relaxometer and a 3D MPI imager at multiple drive field amplitudes and frequencies. Finally, these image measurements are used to estimate relaxation times and nanoparticle phase lags. RESULTS: The authors demonstrate that spatial resolution, as measured by full-width at half-maximum, improves at lower drive field amplitudes. The authors further determine that relaxation in MPI can be approximated as a frequency-independent phase lag. These results enable the authors to accurately predict MPI resolution and sensitivity across a wide range of drive field amplitudes and frequencies. CONCLUSIONS: To balance resolution, signal-to-noise ratio, specific absorption rate, and magnetostimulation requirements, the drive field can be a low amplitude and high frequency. Continued research into how the MPI drive field affects relaxation and its adverse effects will be crucial for developing new nanoparticles tailored to the unique physics of MPI. Moreover, this theory informs researchers how to design scanning sequences to minimize relaxation-induced blurring for better spatial resolution or to exploit relaxation-induced blurring for MPI with molecular contrast.

Magnetic particle imaging with tailored iron oxide nanoparticle tracers.

Magnetic particle imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2(∗) -weighted imaging that are sub-optimal for MPI. Here, we describe new tracers tailored to MPI's unique physics, synthesized using an organic-phase process and functionalized to ensure biocompatibility and adequate in vivo circulation time. Tailored tracers showed up to 3 × greater signal-to-noise ratio and better spatial resolution than existing commercial tracers in MPI images of phantoms.

Magnetic particle imaging (MPI) for NMR and MRI researchers.

Magnetic Particle Imaging (MPI) is a new tracer imaging modality that is gaining significant interest from NMR and MRI researchers. While the physics of MPI differ substantially from MRI, it employs hardware and imaging concepts that are familiar to MRI researchers, such as magnetic excitation and detection, pulse sequences, and relaxation effects. Furthermore, MPI employs the same superparamagnetic iron oxide (SPIO) contrast agents that are sometimes used for MR angiography and are often used for MRI cell tracking studies. These SPIOs are much safer for humans than iodine or gadolinium, especially for Chronic Kidney Disease (CKD) patients. The weak kidneys of CKD patients cannot safely excrete iodine or gadolinium, leading to increased morbidity and mortality after iodinated X-ray or CT angiograms, or after gadolinium-MRA studies. Iron oxides, on the other hand, are processed in the liver, and have been shown to be safe even for CKD patients. Unlike the "black blood" contrast generated by SPIOs in MRI due to increased T2* dephasing, SPIOs in MPI generate positive, "bright blood" contrast. With this ideal contrast, even prototype MPI scanners can already achieve fast, high-sensitivity, and high-contrast angiograms with millimeter-scale resolutions in phantoms and in animals. Moreover, MPI shows great potential for an exciting array of applications, including stem cell tracking in vivo, first-pass contrast studies to diagnose or stage cancer, and inflammation imaging in vivo. So far, only a handful of prototype small-animal MPI scanners have been constructed worldwide. Hence, MPI is open to great advances, especially in hardware, pulse sequence, and nanoparticle improvements, with the potential to revolutionize the biomedical imaging field.

Relaxation in x-space magnetic particle imaging.

Magnetic particle imaging (MPI) is a new imaging modality that noninvasively images the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIOs). MPI has demonstrated high contrast and zero attenuation with depth, and MPI promises superior safety compared to current angiography methods, X-ray, computed tomography, and magnetic resonance imaging angiography. Nanoparticle relaxation can delay the SPIO magnetization, and in this work we investigate the open problem of the role relaxation plays in MPI scanning and its effect on the image. We begin by amending the x-space theory of MPI to include nanoparticle relaxation effects. We then validate the amended theory with experiments from a Berkeley x-space relaxometer and a Berkeley x-space projection MPI scanner. Our theory and experimental data indicate that relaxation reduces SNR and asymmetrically blurs the image in the scanning direction. While relaxation effects can have deleterious effects on the MPI scan, we show theoretically and experimentally that x-space reconstruction remains robust in the presence of relaxation. Furthermore, the role of relaxation in x-space theory provides guidance as we develop methods to minimize relaxation-induced blurring. This will be an important future area of research for the MPI community.

Mitral valve hemodynamics after repair of acute posterior leaflet prolapse: quadrangular resection versus triangular resection versus neochordoplasty.

OBJECTIVE: Leaflet prolapse resulting from acute chordal rupture is one presentation of fibroelastic deficiency that is associated with minimal leaflet changes in the prolapsing segment. Minimizing resection and preserving leaflet tissue may be an optimal surgical strategy. We examined the importance of the leaflet preservation concept by comparing resective and nonresective surgical procedures in practice today. METHODS: Eight porcine mitral valves were evaluated in an in vitro heart simulator before surgical manipulation. Mitral regurgitation was created in these valves by transecting the posterior marginal chordae resulting in severe P2 prolapse. After confirmation of mitral regurgiation via regurgitant flow measurement (mL/beat), regurgitation was corrected by three repairs: neochordoplasty with polytetrafluoroethylene sutures (Gore-Tex; W. L. Gore & Associates, Inc, Flagstaff, Ariz), triangular resection, and quadrangular resection with annular compression. Postrepair valve hemodynamics were quantified under pulsatile conditions of 120 mm Hg peak transmitral pressure and 5 L/min cardiac output at 70 beats/min. Furthermore, hemodynamic, geometric, and echocardiographic indices were measured. RESULTS: Transecting the marginal chordae resulted in severe P2 prolapse and significant mitral regurgiation (19.3 +/- 4.3 mL/beat). Regurgitant volume was significantly reduced after any of the three surgical approaches (quadrangular, 4.38 +/- 1.6 mL/beat; triangular, 2.56 +/- 1.0 mL/beat; neochordal, 2.86 +/- 1.24 mL/beat). In comparison with the baseline normal valves, leaflet coaptation length and posterior leaflet mobility were significantly reduced in the quadrangular resection group, whereas they were partially restored in the triangular resection and fully preserved in the neochordoplasty group. CONCLUSIONS: Although the three repair procedures are hemodynamically comparable, valve function and leaflet kinematics were significantly better after a nonresection or limited resective correction of leaflet prolapse in this experimental model of acute chordal rupture with otherwise normal leaflet geometry.

Saddle shape of the mitral annulus reduces systolic strains on the P2 segment of the posterior mitral leaflet.

BACKGROUND: The three-dimensional saddle shape of the mitral annulus is well characterized in animals and humans, but the impact of annular nonplanarity on valve function or mechanics is poorly understood. In this study, we investigated the impact of the saddle shaped mitral annulus on the mechanics of the P2 segment of the posterior mitral leaflet. METHODS: Eight porcine mitral valves (n = 8) were studied in an in-vitro left heart simulator with an adjustable annulus that could be changed from flat to different degrees of saddle. Miniature markers were placed on the atrial face of the posterior leaflet, and leaflet strains at 0%, 10%, and 20% saddle were measured using dual-camera stereophotogrammetry. Averaged areal strain and the principal strain components are reported. RESULTS: Peak areal strain magnitude decreased significantly from flat to 20% saddle annulus, with a 78% reduction in the measured strain over the entire P2 region. In the radial direction (annulus free edge), a 44.4% reduction in strain was measured, whereas in the circumferential direction (commissure-commissure), a 34% reduction was measured from flat to 20% saddle. CONCLUSIONS: Nonplanar shape of the mitral annulus significantly reduced the mechanical strains on the posterior leaflet during systolic valve closure. Reduction in strain in both the radial and circumferential directions may reduce loading on the suture lines and potentially improve repair durability, and also inhibit progression of valve degeneration in patients with myxomatous valve disease.

Efficacy of the edge-to-edge repair in the setting of a dilated ventricle: an in vitro study.

BACKGROUND: The edge-to-edge repair to correct mitral regurgitation (MR) has shown substandard results in cases of ischemic MR or dilated cardiomyopathy. METHODS: Ten porcine mitral valves were investigated in a left heart simulator (120 mm Hg, 5 L/min). Pathologic conditions of a dilated ventricle were simulated by using an annular model capable of three levels of dilation (normal, 56%, and 120%) and by displacing papillary muscles (PMs) 10 mm in the apical, lateral, and posterior directions. The edge-to-edge repair was performed; a central stitch was investigated for symmetric and asymmetric PM displacements, and a paracommissural stitch was investigated for asymmetric PM displacements. Left ventricular pressure and mitral flow rate were monitored, and regurgitation fraction was calculated from the mitral flow curve. RESULTS: Under symmetric PM displacement, the repair reduced MR by 5.1% at dilation level one and by 9.1% at dilation level two. The repair decreased MR by 10.9% (dilation level two) after asymmetric displacement of the anterior-lateral PM, and by 5.4% (dilation level one) and 7.9% (dilation level two) after asymmetric displacement of the posterior-medial PM. The edge-to-edge repair reduced (p < 0.05) MR owing to annular dilation; however, it was unable to completely eliminate the MR. The repair did not significantly reduce MR caused by PM displacement, regardless of the displacement geometry. Stitch location did not affect repair efficacy. CONCLUSIONS: The edge-to-edge repair is not an effective procedure in correcting MR associated with PM displacement, although it is able to partially reduce MR caused by annular dilation.

Effects of annular size, transmitral pressure, and mitral flow rate on the edge-to-edge repair: an in vitro study.

BACKGROUND: Although edge-to-edge repair is an established adjunctive procedure, there is still debate on its long-term durability and efficacy. METHODS: Fifteen porcine mitral valves were studied in a physiologic left heart simulator with a variable size annulus (dilated = 8.22 cm2, normal = 6.86 cm2, contracted = 5.5 cm2). Mitral valves were tested under steady and physiologic pulsatile flow conditions (cardiac outputs: 4 to 6 L/min), at peak transmitral pressures between 100 mm Hg and 140 mm Hg. A miniature force transducer was used to measure the Alfieri stitch force (F(A)). Mitral flow rate (MFR), transmitral pressure, effective orifice area, mitral regurgitation, and F(A) were monitored. RESULTS: The edge-to-edge repair led to a decrease in effective orifice area of 16.55% +/- 8.22%; further reduction in effective orifice area was attained with annular contraction. Mitral regurgitation after the edge-to-edge repair was significantly higher (p <0.05) with annular dilation. In the pulsatile experiments, two peaks in F(A) were observed: one during systole (F(A) = 0.059 +/- 0.024 N) and a second during diastole (F(A) = 0.072 +/- 0.021 N). Multivariate analysis of variance analysis showed that during systole, transmitral pressure and mitral annular area (MAA) had significant effects on F(A) [F(A) = (4.40 x 10(-4)) transmitral pressure (mm Hg) + (5.0 x 10(-3)) MAA (cm2) - 0.05 (R2 = 0.80)], whereas during diastole MFR and MAA had significant effects on F(A) [F(A) = (1.03 x 10(-4)) MFR2 (L/min) - (1.60 x 10(-3)) MAA (cm2) + 0.02 (R2 = 0.90)]. CONCLUSIONS: With annular dilation, mitral regurgitation persisted even after the edge-to-edge repair. The edge-to-edge repair does not cause clinically relevant mitral valve stenosis in a normal size mitral valve. Mitral flow rate and transmitral pressure are the main determinants of F(A) during the cardiac cycle. Increasing annular area increases F(A) during systole but decreases F(A) during diastole. Systolic F(A) may become dominant with increases in MAA or peak transmitral pressure, or both.