Daniel A. Herzka

Necrotic core thickness and positive arterial remodeling index: Emergent biomechanical factors for evaluating the risk of plaque rupture

Fibrous cap thickness is often considered as diagnostic of the degree of plaque instability. Necrotic core area (Core(area)) and the arterial remodeling index (Remod(index)), on the other hand, are difficult to use as clinical morphological indexes: literature data show a wide dispersion of Core(area) thresholds above which plaque becomes unstable. Although histopathology shows a strong correlation between Core(area) and Remod(index), it remains unclear how these interact and affect peak cap stress (Cap(stress)), a known predictor of rupture. The aim of this study was to investigate the change in plaque vulnerability as a function of necrotic core size and plaque morphology. Cap(stress) value was calculated on 5,500 idealized atherosclerotic vessel models that had the original feature of mimicking the positive arterial remodeling process described by Glagov. Twenty-four nonruptured plaques acquired by intravascular ultrasound on patients were used to test the performance of the associated idealized morphological models. Taking advantage of the extensive simulations, we investigated the effects of anatomical plaque features on Cap(stress). It was found that: 1) at the early stages of positive remodeling, lesions were more prone to rupture, which could explain the progression and growth of clinically silent plaques and 2) in addition to cap thickness, necrotic core thickness, rather than area, was critical in determining plaque stability. This study demonstrates that plaque instability is to be viewed not as a consequence of fibrous cap thickness alone but rather as a combination of cap thickness, necrotic core thickness, and the arterial remodeling index.

Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite

A photoactive hydrogel is used in combination with microfracture to heal cartilage defects in patients. Let There Be Light Light has long been a favorite tool in medicine, finding utility in everything from skin conditions to depression to imaging. Now, Sharma and colleagues have shown that light can be used for biomaterials. Shining light on a hydrogel mixture causes it to polymerize within a defect, thus promoting tissue growth and repairing cartilage in patients. The biomaterial was designed to fill irregular wounds, such as articular cartilage defects. A biological adhesive was applied to the defect, followed by filling with a poly(ethylene glycol) (PEG)–based hydrogel solution. Then, light was applied to polymerize the material to form a solid implant. The hydrogel-adhesive was tested in a large-animal model to see how it worked in combination with the standard procedure for cartilage repair, called microfracture. The surgeons noted that the animals that received the biomaterial along with microfracture had a greater defect fill that was stronger and had more heterogeneous components (cells, proteins, etc.). The authors then moved to testing in people. Fifteen patients with symptomatic cartilage defects were treated with the adhesive-hydrogel after microfracture, whereas three patients were treated with microfracture only. No major adverse events were noted in 6 months after surgery. Similar to the animal studies, the photoactive biomaterial allowed for a greater filling of repair tissue in the defect compared with the control group, with material properties similar to adjacent, healthy cartilage. In addition, hydrogel-treated patients reported a decrease in overall pain severity and frequency over time. Although further clinical testing is needed to compare long-term outcomes in more patients, this light-mediated biomaterial therapy promises to be a versatile and safe way to enhance cartilage repair. Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T2) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects.

Susceptibility gradient mapping (SGM): A new postprocessing method for positive contrast generation applied to superparamagnetic iron oxide particle (SPIO)-labeled cells

Local susceptibility gradients result in a dephasing of the precessing magnetic moments and thus in a fast decay of the NMR signals. In particular, cells labeled with superparamagnetic iron oxide particles (SPIOs) induce hypointensities, making the in vivo detection of labeled cells from such a negative image contrast difficult. In this work, a new method is proposed to selectively turn this negative contrast into a positive contrast. The proposed method calculates the susceptibility gradient and visualizes it in a parametric map directly from a regular gradient‐echo image dataset. The susceptibility gradient map is determined in a postprocessing step, requiring no dedicated pulse sequences or adaptation of the sequence before and during image acquisition. Phantom experiments demonstrated that local susceptibility differences can be quantified. In vivo experiments showed the feasibility of the method for tracking of SPIO‐labeled cells. The method bears the potential also for usage in other applications, including the detection of contrast agents and interventional devices as well as metal implants. Magn Reson Med 60:595–603, 2008.

Fat-Suppression Techniques for 3-T MR Imaging of the Musculoskeletal System

Fat suppression is an important technique in musculoskeletal imaging to improve the visibility of bone-marrow lesions; evaluate fat in soft-tissue masses; optimize the contrast-to-noise ratio in magnetic resonance (MR) arthrography; better define lesions after administration of contrast material; and avoid chemical shift artifacts, primarily at 3-T MR imaging. High-field-strength (eg, 3-T) MR imaging has specific technical characteristics compared with lower-field-strength MR imaging that influence the use and outcome of various fat-suppression techniques. The most commonly used fat-suppression techniques for musculoskeletal 3-T MR imaging include chemical shift (spectral) selective (CHESS) fat saturation, inversion recovery pulse sequences (eg, short inversion time inversion recovery [STIR]), hybrid pulse sequences with spectral and inversion-recovery (eg, spectral adiabatic inversion recovery and spectral attenuated inversion recovery [SPAIR]), spatial-spectral pulse sequences (ie, water excitation), and the Dixon techniques. Understanding the different fat-suppression options allows radiologists to adopt the most appropriate technique for their clinical practice.

Feasibility of image-based simulation to estimate ablation target in human ventricular arrhythmia

BACKGROUND Previous studies suggest that magnetic resonance imaging with late gadolinium enhancement (LGE) may identify slowly conducting tissues in scar-related ventricular tachycardia (VT). OBJECTIVE To test the feasibility of image-based simulation based on LGE to estimate ablation targets in VT. METHODS We conducted a retrospective study in 13 patients who had preablation magnetic resonance imaging for scar-related VT ablation. We used image-based simulation to induce VT and estimate target regions according to the simulated VT circuit. The estimated target regions were coregistered with the LGE scar map and the ablation sites from the electroanatomical map in the standard ablation approach. RESULTS In image-based simulation, VT was inducible in 12 (92.3%) patients. All VTs showed macroreentrant propagation patterns, and the narrowest width of estimated target region that an ablation line should span to prevent VT recurrence was 5.0 ± 3.4 mm. Of 11 patients who underwent ablation, the results of image-based simulation and the standard approach were consistent in 9 (82%) patients, where ablation within the estimated target region was associated with acute success (n = 8) and ablation outside the estimated target region was associated with failure (n = 1). In 1 (9%) case, the results of image-based simulation and the standard approach were inconsistent, where ablation outside the estimated target region was associated with acute success. CONCLUSIONS The image-based simulation can be used to estimate potential ablation targets of scar-related VT. The image-based simulation may be a powerful noninvasive tool for preprocedural planning of ablation procedures to potentially reduce the procedure time and complication rates.

The critical isthmus sites of ischemic ventricular tachycardia are in zones of tissue heterogeneity, visualized by magnetic resonance imaging

BACKGROUND A need exists to develop alternative approaches to VT ablation that provide an improved delineation of the arrhythmogenic substrate. OBJECTIVE The aim of this study was to evaluate the hypotheses that: (1) the heterogeneous zone (HZ, a mixture of normal-appearing tissue and scar) in magnetic resonance imaging (MRI) contains the critical isthmus(es) for ventricular tachycardia (VT), (2) successful ablation of VT would include ablation in the HZ, and (3) inadequate ablation of HZ allows for VT recurrence. METHODS MRI and an electrophysiology study (EP) were performed in a model of chronic myocardial infarction in 17 pigs. In animals that were inducible for VT, ablations were done guided by standard EP criteria and blinded to the MRI. After ablation, electroanatomic mapping results were co-registered with MRI. RESULTS In 8 animals, 22 sustained monomorphic VTs were generated. The HZ was substantially larger in inducible (n = 8) compared with noninducible animals (n = 9) [25% ± 10% vs 13% ± 5% of total scar, respectively, P = .007]. Acutely, all targeted VTs were successfully ablated, and postprocedure analysis showed that at least 1 ablation was in the HZ in each animal. In 5 animals, a second EP and MRI were performed 1 week after ablation. Three animals had inducible VTs, and MRI showed that the HZ had not been completely ablated. In contrast, the 2 animals without inducible VT revealed no remaining HZ. CONCLUSION These findings show that MRI can define an HZ and determine the location of ablated lesions. The HZ may be a promising ablation target to cure ischemic VTs. Remnants of HZ after ablation may be the substrate for clinical relapses.

Adiabatic inversion pulses for myocardial T1-mapping

To evaluate the error in T1 estimates using inversion‐recovery‐based T1 mapping due to imperfect inversion and to perform a systematic study of adiabatic inversion pulse designs in order to maximize inversion efficiency for values of transverse relaxation (T2) in the myocardium subject to a peak power constraint.

Coronary magnetic resonance vein imaging: Imaging contrast, sequence, and timing

Recently, there has been increased interest in imaging the coronary vein anatomy to guide interventional cardiovascular procedures such as cardiac resynchronization therapy (CRT), a device therapy for congestive heart failure (CHF). With CRT the lateral wall of the left ventricle is electrically paced using a transvenous coronary sinus lead or surgically placed epicardial lead. Proper transvenous lead placement is facilitated by the knowledge of the coronary vein anatomy. Cardiovascular MR (CMR) has the potential to image the coronary veins. In this study we propose and test CMR techniques and protocols for imaging the coronary venous anatomy. Three aspects of design of imaging sequence were studied: magnetization preparation schemes (T2 preparation and magnetization transfer), imaging sequences (gradient‐echo (GRE) and steady‐state free precession (SSFP)), and imaging time during the cardiac cycle. Numerical and in vivo studies both in healthy and CHF subjects were performed to optimize and demonstrate the utility of CMR for coronary vein imaging. Magnetization transfer was superior to T2 preparation for contrast enhancement. Both GRE and SSFP were viable imaging sequences, although GRE provided more robust results with better contrast. Imaging during the end‐systolic quiescent period was preferable as it coincided with the maximum size of the coronary veins. Magn Reson Med, 2007.

Myocardial Tagging With SSFP

This work presents the first implementation of myocardial tagging with refocused steady‐state free precession (SSFP) and magnetization preparation. The combination of myocardial tagging (a noninvasive method for quantitative measurement of regional and global cardiac function) with the high tissue signal‐to‐noise ratio (SNR) obtained with SSFP is shown to yield improvements in terms of the myocardium–tag contrast‐to‐noise ratio (CNR) and tag persistence when compared to the current standard fast gradient‐echo (FGRE) tagging protocol. Myocardium–tag CNR and tag persistence were studied using numerical simulations as well as phantom and human experiments. Both quantities were found to decrease with increasing imaging flip angle (α) due to an increased tag decay rate and a decrease in myocardial steady‐state signal. However, higher α yielded better blood–myocardium contrast, indicating that optimal α is dependent on the application: higher α for better blood–myocardium boundary visualization, and lower α for better tag persistence. SSFP tagging provided the same myocardium–tag CNR as FGRE tagging when acquired at four times the bandwidth and better tag– and blood–myocardium CNRs than FGRE tagging when acquired at equal or twice the receiver bandwidth (RBW). The increased acquisition efficiency of SSFP allowed decreases in breath‐hold duration, or increases in temporal resolution, as compared to FGRE. Magn Reson Med 49:329–340, 2003. Published 2003 Wiley‐Liss, Inc.

SPECTRALLY SELECTIVE SUPPRESSION WITH STEADY-STATE FREE PRECESSION

A method is presented that employs the inherent spectral selectivity of the Steady‐State Free Precession (SSFP) pulse sequence to provide a spectral band of suppression. At TE = TR/2, SSFP partitions the magnetization into two phase‐opposed spectral components. Z‐storing one of these components simultaneously further excites the other, which is then suppressed by gradient crushing and RF spoiling. The Spectrally Selective Suppression with SSFP (S5FP) method is shown to provide significant attenuation of fat signals, while the water signals are essentially unaffected and provide the normal SSFP contrast. Fat suppression is achieved with relatively little temporal overhead (less than 10% reduction in temporal resolution). S5FP was validated using simulations, phantoms, and human studies. Magn Reson Med, 2005. Published 2005 Wiley‐Liss, Inc.