Walter R.T. Witschey

Knee Articular Cartilage Damage in Osteoarthritis: Analysis of MR Image Biomarker Reproducibility in ACRIN-PA 4001 Multicenter Trial

PURPOSE To prospectively determine the reproducibility of quantitative magnetic resonance (MR) imaging biomarkers of the morphology and composition (spin lattice relaxation time in rotating frame [T1-ρ], T2) of knee cartilage in a multicenter multivendor trial involving patients with osteoarthritis (OA) and asymptomatic control subjects. MATERIALS AND METHODS This study was HIPAA compliant and approved by the institutional review committees of the participating sites, with written informed consent obtained from all participants. Fifty subjects from five sites who were deemed to have normal knee joints (n = 18), mild OA (n = 16), or moderate OA (n = 16) on the basis of Kellgren-Lawrence scores were enrolled. Each participant underwent four sequential 3-T knee MR imaging examinations with use of the same imager and with 2-63 days (median, 18 days) separating the first and last examinations. Water-excited three-dimensional T1-weighted gradient-echo imaging, T1-ρ imaging, and T2 mapping of cartilage in the axial and coronal planes were performed. Biomarker reproducibility was determined by using intraclass correlation coefficients (ICCs) and root-mean-square coefficients of variation (RMS CVs, expressed as percentages). RESULTS Morphometric biomarkers had high reproducibility, with ICCs of 0.989 or greater and RMS CVs lower than 4%. The largest differences between the healthy subjects and the patients with radiographically detected knee OA were those in T1-ρ values, but precision errors were relatively large. Reproducibility of T1-ρ values was higher in the thicker patellar cartilage (ICC range, 0.86-0.93; RMS CV range, 14%-18%) than in the femorotibial joints (ICC range, 0.20-0.84; RMS CV range, 7%-19%). Good to high reproducibility of T2 was observed, with ICCs ranging from 0.61 to 0.98 and RMS CVs ranging from 4% to 14%. CONCLUSION MR imaging measurements of cartilage morphology, T2, and patellar T1-ρ demonstrated moderate to excellent reproducibility in a clinical trial network.

A technique for in vivo mapping of myocardial creatine kinase metabolism

ATP derived from the conversion of phosphocreatine to creatine by creatine kinase provides an essential chemical energy source that governs myocardial contraction. Here, we demonstrate that the exchange of amine protons from creatine with protons in bulk water can be exploited to image creatine through chemical exchange saturation transfer (CrEST) in myocardial tissue. We show that CrEST provides about two orders of magnitude higher sensitivity compared to 1H magnetic resonance spectroscopy. Results of CrEST studies from ex vivo myocardial tissue strongly correlate with results from 1H and 31P magnetic resonance spectroscopy and biochemical analysis. We demonstrate the feasibility of CrEST measurement in healthy and infarcted myocardium in animal models in vivo on a 3-T clinical scanner. As proof of principle, we show the conversion of phosphocreatine to creatine by spatiotemporal mapping of creatine changes in the exercised human calf muscle. We also discuss the potential utility of CrEST in studying myocardial disorders.

Validation of sodium magnetic resonance imaging of intervertebral disc.

Study Design. This study demonstrated the diagnostic potential of sodium (Na) magnetic resonance imaging (MRI) for noninvasive quantification of proteoglycan (PG) in the intervertebral discs. Objective. To determine the existence of a linear correlation between intervertebral disc [Na] measured from sodium MRI and [PG] measurement from DMMB assay. Summary of Background Data. Previous studies have shown the possibility of quantifying Na in vivo using sodium MRI, however, none has shown a direct linear correlation between Na measured from sodium MRI and in the invertebral discs. Methods. Three-dimensional sodium MRI images of bovine discs were acquired and converted into [Na] maps. Samples were systematically removed from the discs for DMMB assay. The removal locations were photographically recorded and applied to the [Na] maps to extract the [Na] measurements for comparison. In vivo sodium MRI scans were also carried out on a pair of symptomatic and asymptomatic subjects. Results. The linear regression fit of [Na] versus [PG] data yielded a significant linear correlation coefficient of 0.71. The in vivo sodium MRI image of the symptomatic subject showed significant [Na] decrease when compared to that of the asymptomatic subject. Conclusion. Specificity of sodium MRI for PG in the intervertebral discs makes it a promising diagnostic tool for the earlier phase of disc degeneration.

T1ρ-Prepared Balanced Gradient Echo for Rapid 3D T1ρ MRI

To develop a T1ρ‐prepared, balanced gradient echo (b‐GRE) pulse sequence for rapid three‐dimensional (3D) T1ρ relaxation mapping within the time constraints of a clinical exam (<10 minutes), examine the effect of acquisition on the measured T1ρ relaxation time and optimize 3D T1ρ pulse sequences for the knee joint and spine.

Dextran coated bismuth–iron oxide nanohybrid contrast agents for computed tomography and magnetic resonance imaging

Bismuth nanoparticles have been proposed as a novel CT contrast agent, however few syntheses of biocompatible bismuth nanoparticles have been achieved. We herein report the synthesis of composite bismuth-iron oxide nanoparticles (BION) that are based on a clinically approved, dextran-coated iron oxide formulation; the particles have the advantage of acting as contrast agents for both CT and MRI. BION were synthesized and characterized using various analytical methods. BION CT phantom images revealed that the X-ray attenuation of the different formulations was dependent upon the amount of bismuth present in the nanoparticle, while T2-weighted MRI contrast decreased with increasing bismuth content. No cytotoxicity was observed in Hep G2 and BJ5ta cells after 24 hours incubation with BION. The above properties, as well as the yield of synthesis and bismuth inclusion efficiency, led us to select the Bi-30 formulation for in vivo experiments, performed in mice using a micro-CT and a 9.4 T MRI system. X-ray contrast was observed in the heart and blood vessels over a 2 hour period, indicating that Bi-30 has a prolonged circulation half-life. Considerable signal loss in T2-weighted MR images was observed in the liver compared to pre-injection scans. Evaluation of the biodistribution of Bi-30 revealed that bismuth is excreted via the urine, with significant concentrations found in the kidneys and urine. In vitro experiments confirmed the degradability of Bi-30. In summary, dextran coated BION are biocompatible, biodegradable, possess strong X-ray attenuation properties and also can be used as T2-weighted MR contrast agents.

In vivo chronic myocardial infarction characterization by spin locked cardiovascular magnetic resonance.

BackgroundLate gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) is frequently used to evaluate myocardial viability, estimate total infarct size and transmurality, but is not always straightforward is and contraindicated in patients with renal failure because of the risk of nephrogenic systemic fibrosis. T2- and T1-weighted CMR alone is however relatively insensitive to chronic myocardial infarction (MI) in the absence of a contrast agent. The objective of this manuscript is to explore T1ρ-weighted rotating frame CMR techniques for infarct characterization without contrast agents. We hypothesize that T1ρ CMR accurately measures infarct size in chronic MI on account of a large change in T1ρ relaxation time between scar and myocardium.Methods7Yorkshire swine underwent CMR at 8 weeks post-surgical induction of apical or posterolateral myocardial infarction. Late gadolinium enhanced and T1ρ CMR were performed at high resolution to visualize MI. T1ρ-weighted imaging was performed with a B1 = 500 Hz spin lock pulse on a 3 T clinical MR scanner. Following sacrifice, the heart was excised and infarct size was calculated by optical planimetry. Infarct size was calculated for all three methods (LGE, T1ρ and planimetry) and statistical analysis was performed. T1ρ relaxation time maps were computed from multiple T1ρ-weighted images at varying spin lock duration.ResultsMean infarct contrast-to-noise ratio (CNR) in LGE and T1ρ CMR was 2.8 ± 0.1 and 2.7 ± 0.1. The variation in signal intensity of tissues was found to be, in order of decreasing signal intensity, LV blood, fat and edema, infarct and healthy myocardium. Infarct size measured by T1ρ CMR (21.1% ± 1.4%) was not significantly different from LGE CMR (22.2% ± 1.5%) or planimetry (21.1% ± 2.7%; p < 0.05).T1ρ relaxation times were T1ρinfarct = 91.7 ms in the infarct and T1ρremote = 47.2 ms in the remote myocardium.ConclusionsT1ρ-weighted imaging using long spin locking pulses enables high discrimination between infarct and myocardium. T1ρ CMR may be useful to visualizing MI without the need for exogenous contrast agents for a wide range of clinical cardiac applications such as to distinguish edema and scar tissue and tissue characterization of myocarditis and ventricular fibrosis.

T1ρ MRI Quantification of Arthroscopically-Confirmed Cartilage Degeneration

Nine asymptomatic subjects and six patients underwent T1ρ MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2‐3 months postarthroscopy, using sagittal T1‐weighted and axial and coronal T1ρ MRI, from which spatial T1ρ relaxation maps were calculated from segmented T1‐weighted images. Median T1ρ relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (P < 0.001), and median T1ρ exceeded asymptomatic articular cartilage median T1ρ by 2.5 to 9.2 ms. In eight observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1ρ was elevated in five, but in all observations, large foci of increased T1ρ were observed. It was determined that T1ρ could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes. Magn Reson Med 63:1376–1382, 2010.

Three-Dimensional Ultrasound-Derived Physical Mitral Valve Modeling

PURPOSE Advances in mitral valve repair and adoption have been partly attributed to improvements in echocardiographic imaging technology. To educate and guide repair surgery further, we have developed a methodology for fast production of physical models of the valve using novel three-dimensional (3D) echocardiographic imaging software in combination with stereolithographic printing. DESCRIPTION Quantitative virtual mitral valve shape models were developed from 3D transesophageal echocardiographic images using software based on semiautomated image segmentation and continuous medial representation algorithms. These quantitative virtual shape models were then used as input to a commercially available stereolithographic printer to generate a physical model of the each valve at end systole and end diastole. EVALUATION Physical models of normal and diseased valves (ischemic mitral regurgitation and myxomatous degeneration) were constructed. There was good correspondence between the virtual shape models and physical models. CONCLUSIONS It was feasible to create a physical model of mitral valve geometry under normal, ischemic, and myxomatous valve conditions using 3D printing of 3D echocardiographic data. Printed valves have the potential to guide surgical therapy for mitral valve disease.

Rotating Frame Spin Lattice Relaxation in a Swine Model of Chronic, Left Ventricular Myocardial Infarction

T1ρ relaxation times were quantified in a swine model of chronic, left ventricular myocardial infarction. It was found that there were low frequency relaxation mechanisms that suppress endogenous contrast at low spin‐lock amplitudes and in T2‐weighted images. A moderate amplitude spin‐locking pulse could overcome these relaxation mechanisms. Relaxation dispersion data were measured over a range of RF field amplitudes, and a model was formulated to include dipole–dipole relaxation modulated by molecular rotation and an apparent exchange mechanism. These techniques may find some use in the clinic for the observation of chronic, left ventricular cardiac remodeling. Magn Reson Med, 2010.

Localization by nonlinear phase preparation and k‐space trajectory design

A technique is described to localize MR signals from a target volume using nonlinear pulsed magnetic fields and spatial encoding trajectories designed using local k‐space theory. The concept of local k‐space is outlined theoretically, and this principle is applied to simulated phantom and cardiac MRI data in the presence of surface and quadrupolar gradient coil phase modulation. Phantom and in vivo human brain images are obtained using a custom, high‐performance quadrupolar gradient coil integrated with a whole‐body 3‐T MRI system to demonstrate target localization using three‐dimensional T  2* ‐weighted spoiled gradient echo, two‐dimensional segmented, multiple gradient encoded spin echo, and three‐dimensional balanced steady‐state free precession acquisitions. This method may provide a practical alternative to selective radiofrequency excitation at ultra‐high‐field, particularly for steady‐state applications where repetition time (TR) must be minimized and when the amount of energy deposited in human tissues is prohibitive. There are several limitations to the approach including the spatial variation in resolution, high frequency aliasing artifacts, and spatial variation in echo times and contrast. Magn Reson Med, 2012.