Loi Do

Scarred myocardium imposes additional burden on remote viable myocardium despite a reduction in the extent of area with late contrast MR enhancement.

Magnetic resonance imaging (MRI) can simultaneously detect and quantify myocardial dysfunction and shrinkage in contrast-enhanced areas postinfarction. This ability permits the investigation of our hypothesis that transformation of infracted myocardium to scarred tissue imposes additional burdens on peri-infarcted and remote myocardium. Pigs (n=8) were subjected to reperfused infarction. Gd-DOTA-enhanced inversion recovery gradient echo sequence (IR-GRE) imaging was performed 3 days and 8 weeks postinfarction. Global and regional left ventricular (LV) function was evaluated by cine MRI. Triphenyltetrazolium chloride (TTC) stain was used to delineate infarction while hematoxylin and eosin (H & E) and Masson’s trichrome stains were used to characterize remodeled myocardium. Late contrast-enhanced MRIs showed a decrease in the extent of enhanced areas from 17±2% at 3 days to13±1% LV mass at 8 weeks. TTC infarction size was 12±1% LV mass. Cine MRIs showed expansion in dysfunctional area due to unfavorable remodeling, ischemia, or strain. Ejection fraction was reduced in association with increased end-diastolic and end-systolic volumes. Scarred myocardium contained collagen fibers and remodeled thick-walled vessels embedded in collagen. Sequential MRI showed greater LV dysfunction despite the shrinkage in extent of enhanced areas 2 months postinfarction. The integration of late enhancement and cine MRI incorporates anatomical and functional evaluation of remodeled hearts.

MR Assessment of Myocardial Perfusion, Viability, and Function after Intramyocardial Transfer of VM202, a New Plasmid Human Hepatocyte Growth Factor in Ischemic Swine Myocardium

PURPOSE VM202, a newly constructed plasmid human hepatocyte growth factor, was transferred intramyocardially after infarction for the purpose of evaluating this strategy as a therapeutic approach for protection from left ventricular (LV) remodeling. MATERIALS AND METHODS The institutional animal care and use committee approved this study. Pigs underwent coronary artery occlusion and reperfusion and served as either control (n = 8) or VM202-treated (n = 8) animals. VM202 was transferred intramyocardially into four infarcted and four periinfarcted sites. Cardiac magnetic resonance (MR) imaging (cine, perfusion, delayed enhancement) was performed in acute (3 days) and chronic (50 days +/- 3 [standard error of the mean]) infarction. Histopathologic findings were used to characterize and quantify neovascularization. The t test was utilized to compare treated and control groups and to assess changes over time. RESULTS In acute infarction, MR imaging estimates of function, perfusion, and viability showed no difference between the groups. In chronic infarction, however, VM202 increased maximum signal intensity and upslope at first-pass perfusion imaging and reduced infarct size at perfusion and delayed-enhancement imaging. These changes were associated with a decrease in end-diastolic (2.15 mL/kg +/- 0.12 to 1.73 mL/kg +/- 0.10, P < .01) and end-systolic (1.33 mL/kg +/- 0.07 to 0.92 mL/kg +/- 0.08, P < .001) volumes and an increase in ejection fraction (38.2% +/- 1.3 to 47.0% +/- 1.8, P < .001). In contrast, LV function deteriorated further in control animals. Compared with control animals, VM202-treated animals revealed peninsulas and/or islands of viable myocardium in infarcted and periinfarcted regions and greater number of capillaries (218 per square millimeter +/- 19 vs 119 per square millimeter +/- 17, P < .05) and arterioles (21 per square millimeter +/- 4 vs 3 per square millimeter +/- 1, P < .001). CONCLUSION Intramyocardial transfer of VM202 improved myocardial perfusion, viability, and LV function.

CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine

Delivery of resiniferatoxin under CT guidance around lumbar dorsal root ganglia in pigs resulted in selective deletion of nociceptive neurons and lasting analgesia. Improved pain control with a spicy chili pepper variant Chronic severe pain can be agonizing, and methods to control it are often inadequate or limited by side effects. Brown et al. used a CT scanner to guide needles through the skin of swine directly to pain-transmitting nerve fibers. Through these needles, they injected resiniferatoxin, which is a very powerful variant of capsaicin, the spicy ingredient in chili peppers. This drug is toxic to cells that carry its receptor (TRPV1), which are almost exclusively pain-transmitting neurons. This enabled the authors to selectively block pain transmission in pigs without affecting “bystander” nerves carrying other sensory information. One approach to analgesia is to block pain at the site of origin or along the peripheral pathway by selectively ablating pain-transmitting neurons or nerve terminals directly. The heat/capsaicin receptor (TRPV1) expressed by nociceptive neurons is a compelling target for selective interventional analgesia because it leaves somatosensory and proprioceptive neurons intact. Resiniferatoxin (RTX), like capsaicin, is a TRPV1 agonist but has greater potency. We combine RTX-mediated inactivation with the precision of computed tomography (CT)–guided delivery to ablate peripheral pain fibers in swine. Under CT guidance, RTX was delivered unilaterally around the lumbar dorsal root ganglia (DRG), and vehicle only was administered to the contralateral side. During a 4-week observation period, animals demonstrated delayed or absent withdrawal responses to infrared laser heat stimuli delivered to sensory dermatomes corresponding to DRG receiving RTX treatment. Motor function was unimpaired as assessed by disability scoring and gait analysis. In treated DRG, TRPV1 mRNA expression was reduced, as were nociceptive neuronal perikarya in ganglia and their nerve terminals in the ipsilateral dorsal horn. CT guidance to precisely deliver RTX to sites of peripheral pain transmission in swine may be an approach that could be tailored to block an array of clinical pain conditions in patients.

Impaired regional left ventricular strain after repair of tetralogy of Fallot.

To test the potential of magnetic resonance imaging (MRI) in early detection of left ventricular (LV) dysfunction in patients with pulmonary regurgitation and normal LV ejection fraction after repair of tetralogy of Fallot.

Endovascular Catheter for Magnetic Navigation under MR Imaging Guidance: Evaluation of Safety In Vivo at 1.5T

BACKGROUND AND PURPOSE: Endovascular navigation under MR imaging guidance can be facilitated by a catheter with steerable microcoils on the tip. Not only do microcoils create visible artifacts allowing catheter tracking, but also they create a small magnetic moment permitting remote-controlled catheter tip deflection. A side product of catheter tip electrical currents, however, is the heat that might damage blood vessels. We sought to determine the upper boundary of electrical currents safely usable at 1.5T in a coil-tipped microcatheter system. MATERIALS AND METHODS: Alumina tubes with solenoid copper coils were attached to neurovascular microcatheters with heat shrink-wrap. Catheters were tested in carotid arteries of 8 pigs. The catheters were advanced under x-ray fluoroscopy and MR imaging. Currents from 0 mA to 700 mA were applied to test heating and potential vascular damage. Postmortem histologic analysis was the primary endpoint. RESULTS: Several heat-mitigation strategies demonstrated negligible vascular damage compared with control arteries. Coil currents ≤300 mA resulted in no damage (0/58 samples) compared with 9 (25%) of 36 samples for > 300-mA activations (P = .0001). Tip coil activation ≤1 minute and a proximal carotid guide catheter saline drip > 2 mL/minute also had a nonsignificantly lower likelihood of vascular damage. For catheter tip coil activations ≤300 mA for ≤1 minute in normal carotid flow, 0 of 43 samples had tissue damage. CONCLUSIONS: Activations of copper coils at the tip of microcatheters at low currents in 1.5T MR scanners can be achieved without significant damage to blood vessel walls in a controlled experimental setting. Further optimization of catheter design and procedure protocols is necessary for safe remote control magnetic catheter guidance.

Permanent coronary artery occlusion: cardiovascular MR imaging is platform for percutaneous transendocardial delivery and assessment of gene therapy in canine model.

PURPOSE To provide evidence that vascular endothelial growth factor (VEGF) genes delivered transendocardially with magnetic resonance (MR) imaging guidance may neovascularize or improve vascular recruitment in occlusive infarction. MATERIALS AND METHODS All experimental procedures received approval from the institutional committee on animal research. Dogs with permanent coronary artery occlusion were imaged twice (3 days after occlusion for assessment of acute infarction; a mean of 50 days after occlusion +/- 3 [standard error of the mean] for assessment of chronic infarction). A mixture of plasmid VEGF and plasmid LacZ (n = 6, treated animals) or plasmid LacZ and sprodiamide (n = 6, placebo control animals) was delivered to four sites. MR fluoroscopy was used to target and monitor delivery of genes. The effectiveness of this delivery approach was determined by using MR imaging methods to assess perfusion, left ventricular (LV) function, myocardial viability, and infarct resorption. Histologic evaluation of neovascularization was then performed. RESULTS MR fluoroscopic guidance of injectates was successful in both groups. Treated animals with chronic, but not those with acute, infarction showed the following differences compared with control animals: (a) steeper mean maximum upslope perfusion (200 sec(-1) +/- 32 vs 117 sec(-1) +/- 15, P = .02), (b) higher peak signal intensity (1667 arbitrary units +/- 100 vs 1132 arbitrary units +/- 80, P = .002), (c) increased ejection fraction (from 27.9% +/- 1.2 to 35.3% +/- 1.6, P = .001), (d) smaller infarction size (as a percentage of LV mass) at MR imaging (8.5% +/- 0.9 vs 11.3% +/- 0.9, P = .048) and triphenyltetrazolium chloride staining (9.4% +/- 1.5 vs 12.7% +/- 0.4, P = .05), and (e) higher vascular density (as number of vessels per square millimeter) at the border (430 +/- 117 vs 286 +/- 19, P = .0001) and core (307 +/- 112 vs 108 +/- 17, P = .0001). CONCLUSION The validity of plasmid VEGF gene delivered with MR fluoroscopic guidance into occlusive infarction was confirmed by neovascularization associated with improved perfusion, LV function, and infarct resorption.

Coronary Microemboli Effects in Preexisting Acute Infarcts in a Swine Model: Cardiac MR Imaging Indices, Injury Biomarkers, and Histopathologic Assessment

PURPOSE To use cardiac magnetic resonance (MR) imaging indices, injury biomarkers, and microscopy for quantifying the effects of defined microemboli volume and sizes on viability, left ventricular (LV) function, and perfusion in preexisting acute myocardial infarcts in a swine model. MATERIALS AND METHODS Institutional approval was obtained to perform x-ray fluoroscopy and 90-minute left anterior descending coronary artery occlusion-reperfusion (single ischemic insult) in 16 pigs and coronary embolization in eight of the 16 pigs (32 mm(3), 40-120 μm microemboli) (double ischemic insults). Another eight pigs served as controls. Cardiac MR imaging results (viability, function, and perfusion), injury biomarkers (creatine-kinase-MB and troponin I), and histopathologic evaluations were quantified. Analysis of variance was performed, and a P value less than .02 was considered to indicate a significant difference. RESULTS Delayed contrast material-enhanced MR imaging allowed simultaneous visualization of hyperenhanced large infarcts, hypoenhanced microvascular obstruction (MVO) zones, and moderately enhanced patchy microinfarcts in border zones, which represent different degrees of contraction and perfusion in the respective regions, in pigs subjected to double ischemic insults. The increase in myocardial damage was smaller in pigs with double insults (15.7% ± 1.1% of total LV mass) than in those with a single insult (12.4% ± 1.2%, P < .02), but the reduction in LV ejection fraction was disproportional (32% ± 0.6% and 38% ± 1%, P < .02, respectively). Delayed contrast-enhanced imaging can allow quantification of the MVO zone but can result in underestimation of the extent of myocardial damage compared with microscopy in animals subjected to double insults (18.2 ± 1.6, P < .02). A significant increase in cardiac injury biomarkers was observed at 18-24 hours in both cohorts. The additional effect of microemboli on troponin I was demonstrated at 68-72 hours (3.2 ng/mL ± 0.85 [3.20 μg/L ± 0.85] vs 1.34 ng/mL ± 0.43 [1.34 μg/L ± 0.43], P < .02). CONCLUSION MR imaging has the potential to allow visualization of acute myocardial infarcts, MVO zones, and patchy microinfarcts simultaneously. The accentuated LV dysfunction caused by double ischemic insults was linked to expansion of the MVO zone, perfusion deficits, and myocardial damage.

MRI study on volume effects of coronary emboli on myocardial function, perfusion and viability

BACKGROUND Coronary filtration devices showed inadequate protection during PCI due to the inability to filter microemboli <120 μm in diameter. The purpose of this study was to determine the impact of two volumes of <120 μm microemboli on LV function, perfusion and viability using magnetic resonance imaging (MRI). METHODS Under X-ray guidance, pigs (n = 18) received two different volumes (16 mm(3) or 32 mm(3)) of 40-120 μm microemboli (intracoronary). At 3 days, regional myocardial perfusion and LV function were assessed using first pass perfusion and cine MRI. Viability MRI was performed in beating and non-beating hearts to delineate microinfarcts and compare with histochemical triphenyltetrazolium chloride stain, using semi-automatic threshold method. Histology and cardiac injury enzymes were used to confirm the presence of microinfarcts and characterize cellular and vascular changes. RESULTS Microinfarcts were visible as enhanced specks on DE-MRI in all animals that received 32 mm(3), but only two-third of the animals that received 16 mm(3), volume. The decline in ejection fraction and increase in LV volumes and microinfarcts were volume dependent. Regional perfusion and contractility were significantly reduced in the LAD territory compared with remote myocardium. Histology showed apoptosis, edema, inflammation and vascular thrombosis. CONCLUSIONS Microemboli of <120 μm have deleterious effects on LV function, perfusion and viability and the effects are dependent on microemboli volume. Microinfarct visualization is crucial to ensure that myocardial dysfunction is related to dislodged microemboli and not only to pre-procedural stunning or hibernation. This noninvasive MRI method may help in evaluating the effectiveness of coronary filtration devices in protecting myocardium from microemboli.

MRI-guided high-intensity focused ultrasound ablation of bone: Evaluation of acute findings with MR and CT imaging in a swine model

To evaluate hyperacute (<1 hour) changes on magnetic resonance (MR) and computed tomography (CT) imaging following MR‐guided high‐intensity focused ultrasound (MRgHIFU) in a swine bone model as a function of sonication number and energy.

MRI demonstrates a decrease in myocardial infarct healing and increase in compensatory ventricular hypertrophy following mechanical microvascular obstruction

To provide direct evidence that mechanical obstruction of microvessels inhibits infarct resorption (healing) and enhances left ventricular (LV) remodeling using MRI.