An experimental model of chronic severe mitral regurgitation.

Objective: To develop a minimally invasive, reproducible model of chronic severe mitral regurgitation (MR) that replicates the clinical phenotype of left atrial (LA) and left ventricular dilation and susceptibility to atrial fibrillation. Methods: Under transesophageal echocardiographic guidance, chordae tendinae were avulsed using endovascular forceps until the ratio of regurgitant jet area to LA area was ≥70%. Animals survived for an average of 8.6 ± 1.6 months (standard deviation) and imaged with monthly transthoracic echocardiography (TTE). Animals underwent baseline and preterminal magnetic resonance imaging. Terminal studies included TTE, transesophageal echocardiography, and rapid atrial pacing to test inducibility of atrial tachyarrhythmias. Results: Eight dogs underwent creation of severe MR and interval monitoring. Two were excluded-one died from acute heart failure, and the other had resolution of MR. Six dogs underwent the full experimental protocol; only one required medical management of clinical heart failure. MR remained severe over time, with a mean terminal regurgitant jet area to LA area of 71 ± 14% (standard deviation) and regurgitant fraction of 52 ± 11%. Mean LA volume increased over 130% (TTE: 163 ± 147%, P = .039; magnetic resonance imaging: 132 ± 54%, P = .011). Mean left ventricular end-diastolic volume increased by 38 ± 21% (P = .008). Inducible atrial tachyarrhythmias were seen in 4 of 6 animals at terminal surgery, and none at baseline. Conclusions: Within the 6 dogs that successfully completed the full experimental protocol, this model replicated the clinical phenotype of severe MR, which led to marked structural and electrophysiologic cardiac remodeling. This model allowed for precise measurements at repeated time points and will facilitate future studies to elucidate the mechanisms of atrial and ventricular remodeling secondary to MR and the pathophysiology of valvular atrial fibrillation.

The Feasibility of Using Volumetric Phase-Contrast MR Imaging (4D Flow) to Assess for Transjugular Intrahepatic Portosystemic Shunt Dysfunction.

PURPOSE: To demonstrate the feasibility of detecting patency, stenosis, or occlusion of transjugular intrahepatic portosystemic shunt (TIPS) with four-dimensional (4D) flow MR imaging. MATERIALS AND METHODS: Sequential adult patients with TIPS were eligible for enrollment. Volumetric phase-contrast sequence was used to image TIPS. Particle tracing cine images were used for qualitative assessment of stenosis. TIPS was segmented to generate quantitative data sets of peak velocity. Segmentation and quantitative measurement of flow throughout an entire TIPS defined technical success. Doppler US was used for comparison. Venography, when available, and 6-month clinical follow-up were used as reference standards. RESULTS: 4D flow MR imaging was performed in 23 patient encounters and was technically successful in 16/23 (69.6%) encounters. Three cases demonstrated both focal turbulence and abnormal velocities (> 190 cm/s or < 90 cm/s) on 4D flow and had venography-confirmed stenosis (true-positive cases). Seven cases had normal velocities and no turbulence on 4D flow, and all were confirmed negative with clinical follow-up or venography (true-negative cases). Six cases had discordant 4D flow results, with abnormal velocities but no turbulence or focal turbulence but normal velocities. All 6 discordant cases had no evidence of dysfunction during 6-month follow-up. CONCLUSION: 4D flow MR imaging can detect TIPS patency and stenosis, but further investigation is required before it can be used to assess for TIPS dysfunction.

Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials.

BACKGROUND AND OBJECTIVE: Dysferlinopathies are a group of muscle disorders caused by mutations in the DYSF gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests. METHODS: We present cross-sectional T1-weighted muscle MRI data from 182 patients with genetically confirmed dysferlinopathies. We have analysed the pattern of muscles involved in the disease using hierarchical analysis and presented it as heatmaps. Results of the MRI scans have been correlated with relevant functional tests for each region of the body analysed. RESULTS: In 181 of the 182 patients scanned, we observed muscle pathology on T1-weighted images, with the gastrocnemius medialis and the soleus being the most commonly affected muscles. A similar pattern of involvement was identified in most patients regardless of their clinical presentation. Increased muscle pathology on MRI correlated positively with disease duration and functional impairment. CONCLUSIONS: The information generated by this study is of high diagnostic value and important for clinical trial development. We have been able to describe a pattern that can be considered as characteristic of dysferlinopathy. We have defined the natural history of the disease from a radiological point of view. These results enabled the identification of the most relevant regions of interest for quantitative MRI in longitudinal studies, such as clinical trials. CLINICAL TRIAL REGISTRATION: NCT01676077.

Resonant forcing of multidimensional chaotic map dynamics.

We study resonances of chaotic map dynamics. We use the calculus of variations to determine the additive forcing function that induces the largest response. We find that resonant forcing functions complement the separation of nearby trajectories, in that the product of the displacement of nearby trajectories and the resonant forcing is a conserved quantity. As a consequence, the resonant function will have the same periodicity as the displacement dynamics, and if the displacement dynamics is irregular, then the resonant forcing function will be irregular as well. Furthermore, we show that resonant forcing functions of chaotic systems decrease exponentially, where the rate equals the negative of the largest Lyapunov exponent of the unperturbed system. We compare the response to optimal forcing with random forcing and find that the optimal forcing is particularly effective if the largest Lyapunov exponent is significantly larger than the other Lyapunov exponents. However, if the largest Lyapunov exponent is much larger than unity, then the optimal forcing decreases rapidly and is only as effective as a single-push forcing.

Hybrid peripheral 3D contrast-enhanced MR angiography of calf and foot vasculature.

OBJECTIVE: The objective of our study was to describe hybrid peripheral (HyPer) 3D contrast-enhanced MR angiography (CE-MRA) using sagittal acquisition with parallel imaging of the calf and foot station. The benefit of a dedicated sagittal 3D CE-MRA acquisition of the calf and foot was evaluated by assessing the degree of venous contamination and its diagnostic quality compared with standard bolus chase 3D CE-MRA alone. MATERIALS AND METHODS: Fifty-three patients (99 legs) were scanned with a 1.5-T MR system equipped with a dedicated bilateral lower extremity phased-array coil. First, high-resolution 3D CE-MRA images of the calves and feet were obtained using two separate sagittal slabs with parallel imaging, with a resulting voxel size of 1.4 x 1.0 x 1.0 mm3. Second, standard bolus chase 3D CE-MRA was performed from the abdomen and pelvis station to the calf-foot station. Images were interpreted by two radiologists. The calf-foot arterial trees were divided into 12 segments. Each segment was characterized as diagnostic or nondiagnostic. The degree of venous contamination was assessed as interfering with the diagnosis or not. Paired Student's t test and Wilcoxon's signed rank test were used to test for statistically significant differences between the techniques. RESULTS: For the left leg (n = 48), the mean number (+/- SD) of diagnosed arterial segments for HyPer 3D CE-MRA was 9.2 +/- 2.3 and for bolus chase 3D CE-MRA, 7.1 +/- 4.2 (p < or = 0.0004). For the right leg (n = 51), the corresponding values were 9.4 +/- 2.2 and 7.6 +/- 3.5 (p < or = 0.0005), respectively. For bolus chase 3D CE-MRA, venous contamination interfered with the diagnosis in 24 of 99 legs, whereas with HyPer 3D CE-MRA, there was no interference. Selective analysis of the dorsalis pedis arteries showed that the number of diagnostic vessels was 62 (62.6%) of 99 for HyPer 3D CE-MRA and 13 (13.1%) of 99 for bolus chase 3D CE-MRA. CONCLUSION: HyPer 3D CE-MRA is an alternative method for time-resolved high-resolution peripheral CE-MRA in evaluating the trifurcation and feet vessels with no venous contamination.

Dynamic coronary MR angiography and first-pass perfusion with intracoronary administration of contrast agent.

PURPOSE: To evaluate whether dynamic imaging of the coronary arteries can be performed with intracoronary infusion of low-dose gadolinium (Gd)-based contrast agent and assess the effect of long duration and multiple infusions on the image signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). MATERIALS AND METHODS: Dynamic coronary magnetic resonance (MR) imaging (130 msec/image) and contrast agent first pass myocardial perfusion studies were performed with intracoronary infusions of low-dose Gd-based MR contrast agent on dogs (N = 4) using a fast multislice gradient recalled echo (GRE) sequence. RESULTS: Contrast-enhanced coronary arteries were clearly imaged during infusion periods as long as 2.3 minutes. The SNR and CNR of the contrast-enhanced coronary arteries remained essentially unchanged over multiple consecutive angiographic sessions. In addition, we demonstrated that first pass studies performed with intracoronary injection of MR contrast agent can be used as a means of assessing regional myocardial perfusion. CONCLUSION: These studies demonstrated that, using intracoronary infusion of Gd, coronary magnetic resonance angiography (MRA) can be performed with high temporal resolution, and multiple low-dose slow infusions of Gd-based MR contrast agent can be performed without compromise of the vessel SNR and CNR.