Abnormal diastolic and systolic septal motion following pericardiectomy demonstrated by ciné DENSE MRI.

Constrictive pericarditis can lead to paradoxical interventricular septal motion. Displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) provides a method for quantifying myocardial motion and strain. A case of constrictive pericarditis is presented and the diastolic 'septal bounce' is clearly evident in both anatomical and DENSE ciné MRI images. (See video link to full-text electronic article). The postoperative systolic septal wall-motion abnormality of cardiac surgery is portrayed with greater precision by DENSE than anatomical ciné MRI images.

Post-ischaemic myocardial dysfunction (stunning) results from myofibrillar oedema.

OBJECTIVE: To test the hypothesis that myocardial stunning is due to myofibrillar oedema. METHODS: Experiments were performed in anaesthetised closed-chest pigs. In 15 pigs (group 1), myocardial stunning was produced by repetitive ischaemia and reperfusion; 5 pigs each were studied at 2 hours, 2 days, and 5 days later. Circumferential left ventricular (LV) mid-wall myocardial strain (E(cc)) was estimated in vivo using tagged magnetic resonance imaging. Myocardial water content (MWC) was measured post mortem, from which interfilament lattice distance (d) was calculated. In 6 pigs (group 2), myocardial dysfunction was produced by intracoronary administration of a mast cell degranulator. Animals were euthanised immediately upon induction of regional LV dysfunction to avoid development of inflammation. In 4 pigs (group 3), transmission electron microscopy (EM) was performed to quantify d in stunned versus normal myocardium. RESULTS: In group 1 pigs, MWC was raised in the stunned compared with normal myocardium (p<0.02) and decreased over time. An inverse relation was found between E(cc) and MWC in the stunned myocardium (r = -0.81) and between E(cc) and d (r = -0.90). A similar relation was noted between wall thickening and increase in MWC in group 2 (r = -0.84) pigs. In group 3 pigs, d on EM was significantly lower (40 (3) nmol/l) in normal myocardium than in stunned myocardium (46.4 (4) nmol/l), p<0.001. CONCLUSIONS: Ischaemia-reperfusion results in myocardial oedema, with consequent myocyte swelling and myofibrillar oedema. The latter leads to an increase in d, causing myosin heads to either fail to latch, or to latch improperly, onto the actin filament with poor force generation, leading to myocardial dysfunction. As the myocardial oedema abates, myocyte function improves.

Placental ischemia and soluble fms-like tyrosine kinase 1: cause or consequence of preeclampsia?

Elevated circulating soluble fms-like tyrosine kinase 1 (sFLT-1) is associated with the development of the clinical signs and symptoms of preeclampsia. Placental ischemia has been suggested as one of the etiological factors that mediate increased sFLT-1 production in patients with preeclampsia, but definitive evidence for this hypothesis was lacking. Makris et al. demonstrate that inducing placental ischemia in primates is sufficient to induce sFLT-1 upregulation and the clinical signs and symptoms of preeclampsia.

Role of the cytoskeleton in secretion of chloride by shark rectal gland.

The salt gland of the spiny dogfish, Squalus acanthias, can be stimulated to secrete chloride by two different endogenous peptides: cardiac natriuretic peptide (CNP) and the neurotransmitter, vasoactive intestinal peptide (VIP). We examined the role of the actin cytoskeleton and of myosin light chains in this process by perfusing isolated rectal glands with and without an inhibitor of actin filament organization (cytochalasin D) and an inhibitor of myosin light chain kinase (ML-7). Cytochalasin D, 10(-6) M, reduced secretion stimulated by a 1-min bolus of CNP (5x10(-7) M) by 50-60%. In the presence of 10(-2) M procaine (which blocks neural release of VIP), cytochalasin D completely prevented CNP stimulation. In contrast, cytochalasin D did not inhibit stimulation of the rectal gland by VIP or by forskolin. Similarly, 5x10(-6)M ML-7 almost completely inhibited direct stimulation of rectal gland secretion by CNP, but did not alter chloride secretion induced by VIP or forskolin. Finally, the average time between hormonal injection and activation of secretion was 2 min longer for CNP than for VIP, consistent with the hypothesis that a contractile cellular function involving the cytoskeleton is important in CNP-induced chloride secretion, but less so when secretion is stimulated by VIP.

Changes in intrarenal oxygenation as evaluated by BOLD MRI in a rat kidney model for radiocontrast nephropathy.

The pathogenesis of radiocontrast nephropathy is poorly understood. In an animal model, inhibition of the synthesis of nitric oxide and prostaglandins appears to predispose rats to severe renal injury following the administration of radiocontrast. Here we have investigated whether administration of radiocontrast, as well as changes in renal medullary oxygenation following pharmacologic inhibition of nitric oxide and prostaglandin synthesis, might be evaluated by blood oxygenation level-dependent (BOLD) MRI. Nineteen anesthetized (Inactin 100 mg/kg) rats were studied. BOLD MRI measurements were performed following administration of L-NAME (N-nitro-L-arginine methyl ester, 10 mg/kg), Indomethacin (10 mg/kg), and a radiocontrast agent (sodium iothalamate 60%, 6 mL/kg). Marked sequential changes in medullary R(*)(2), presumably reflecting decline in medullary pO(2), were noted after each of the pharmacological interventions employed. These results, obtained by noninvasive MRI, are consistent with prior direct recordings of pO(2) and doppler flow in the rat renal medulla after administration of L-NAME, Indomethacin and iothalamate. Medullary oxygenation in rats was reduced by inhibition of the synthesis of prostaglandins and nitric oxide, as well as by intravenous injection of radiocontrast agents. BOLD MRI can noninvasively evaluate changes in medullary oxygenation in rats that appear to predispose acute renal failure. J. Magn. Reson. Imaging 2001;13:744-747.

Myocardial wall tagging with undersampled projection reconstruction.

Azimuthally undersampled projection reconstruction (PR) acquisition is investigated for use in myocardial wall tagging with MR using grid tags to provide increased temporal and spatial resolution. PR can provide the high-resolution images required for tagging with very few projections, at the expense of artifact. Insight is provided into the PR undersampling artifact, in the context of measuring myocardial motion with tags. For Fourier transform imaging, at least 112 phase-encodings must be collected to image tagging grids spaced 7 pixels apart. PR requires about 80 projections, a 1.4-fold reduction in scan time. Magn Reson Med 45:562-567, 2001. Published 2001 Wiley-Liss, Inc.

Adaptive sensitivity encoding incorporating temporal filtering (TSENSE).

A number of different methods have been demonstrated which increase the speed of MR acquisition by decreasing the number of sequential phase encodes. The UNFOLD technique is based on time interleaving of k-space lines in sequential images and exploits the property that the outer portion of the field-of-view is relatively static. The differences in spatial sensitivity of multiple receiver coils may be exploited using SENSE or SMASH techniques to eliminate the aliased component that results from undersampling k-space. In this article, an adaptive method of sensitivity encoding is presented which incorporates both spatial and temporal filtering. Temporal filtering and spatial encoding may be combined by acquiring phase encodes in an interleaved manner. In this way the aliased components are alternating phase. The SENSE formulation is not altered by the phase of the alias artifact; however, for imperfect estimates of coil sensitivities the residual artifact will have alternating phase using this approach. This is the essence of combining temporal filtering (UNFOLD) with spatial sensitivity encoding (SENSE). Any residual artifact will be temporally frequency-shifted to the band edge and thus may be further suppressed by temporal low-pass filtering. By combining both temporal and spatial filtering a high degree of alias artifact rejection may be achieved with less stringent requirements on accuracy of coil sensitivity estimates and temporal low-pass filter selectivity than would be required using each method individually. Experimental results that demonstrate the adaptive spatiotemporal filtering method (adaptive TSENSE) with acceleration factor R = 2, for real-time nonbreath-held cardiac MR imaging during exercise induced stress are presented.

Is imaging at intermediate doses necessary during dobutamine stress magnetic resonance imaging?

To determine if visualization of left ventricular contraction throughout the course of a pharmacologic stress test performed with magnetic resonance imaging (MRI) (rather than solely at baseline and peak stress) is necessary, we retrospectively reviewed dobutamine MRI results in 469 consecutively referred patients for diagnosis of inducible ischemia. At each stage of pharmacologic stress, six image planes of the heart were viewed and left ventricular wall motion was scored as normal, hypokinetic, akinetic, or dyskinetic. Inducible ischemia was identified in 102 patients; in 39 patients (38%), evidence of ischemia occurred before receiving high doses of dobutamine. During testing, 103 patients developed chest discomfort consistent with angina, but only 26 of the 103 patients (25%) developed new wall motion abnormalities indicative of ischemia. Continuous image acquisition and review during dobutamine MRI pharmacologic stress testing provides a mechanism to detect ischemia and avoid premature test termination during the early stages of the procedure. Compared with protocols that image only at baseline and at peak stress, continuous acquisition and review may enhance the safety and improve the diagnostic accuracy of pharmacologic stress testing during dobutamine MRI.

New and old perspectives on acute renal failure.

The pathophysiology, course, and treatment of acute renal failure in humans differs substantially from the ischemia/reflow model of renal injury commonly studied in rats and mice. Acute renal failure in humans is best understood as the result of an exacerbation of the usual state of hypoxia in the renal medulla and medullary rays, leading to reversible tubular dysfunction and glomerular vasoconstriction. A secondary inflammatory cascade may also play an important role, though this has not yet been clearly shown in patients.

Low-latency temporal filter design for real-time MRI using UNFOLD.

To improve real-time control of interventional procedures such as guidance of catheters, monitoring of ablation therapy, or control of dosage during drug delivery, the image acquisition and reconstruction must be high speed and have low latency (small time delay) in processing. A number of different methods have been demonstrated which increase the speed of MR acquisition by decreasing the number of sequential phase-encodes. A design and implementation of the UNFOLD method which achieves the desired low latency with a recursive temporal filter is presented. The recursive filter design is characterized for this application and compared with more commonly used moving average filters. Experimental results demonstrate low-latency UNFOLD for two applications: 1) high-speed, real-time imaging of the heart to be used in conjunction with cardiac interventional procedures; and 2) the injection of drugs into muscle tissue with contrast enhancement, i.e., monitoring needle insertion and injection of a drug with contrast enhancement properties. Proof-of-concept was demonstrated by injecting a contrast agent. In both applications the UNFOLD technique was used to double the frame rate.

Effects of furosemide on medullary oxygenation in younger and older subjects.

UNLABELLED: Renal medullary hypoxia is characteristic of mammalian kidneys and can be assessed noninvasively in animals and humans by blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). Water diuresis has been shown to improve medullary oxygenation in young human subjects but not in elderly subjects, a difference attributed to a decline in renal prostaglandin production with age. Loop diuretics such as furosemide also increase medullary oxygenation in experimental animals, by inhibiting active transport and oxygen consumption in the medullary thick ascending limb. We examined, using BOLD MRI, this response to furosemide in eight younger (23 to 34 years) and eight elderly (64 to 81 years) healthy women. We also attempted to assess the role of prostaglandins in age-related differences, using ibuprofen to inhibit prostaglandin E2 synthesis. Renal medullary oxygenation, initially low, increased during furosemide diuresis in younger subjects. In the older population, however, furosemide usually elicited little or no change in oxygenation of the renal medulla, despite profuse diuresis. Ibuprofen did not inhibit the action of furosemide to improve medullary pO2 in younger subjects. CONCLUSIONS: The action of loop diuretics to improve medullary oxygenation, apparent in younger subjects, is blunted by normal aging. Inhibition of prostaglandin synthesis did not counteract the effect of furosemide in younger subjects, suggesting that a decline in prostaglandin E2 production with age is not the central cause of this age-related defect.

Optimization of fast cardiac imaging using an echo-train readout.

Fast gradient-echo sequences that use an echo-train readout are becoming more widely used, particularly for imaging the heart. An important issue for these sequences involves determining the optimal duration for the echo-train readout. In normal volunteer scans and theoretically the echo-train readout duration was varied from 2.4 to 32.8 msec. Myocardial signal-to-noise ratio (SNR), myocardium-tag signal difference-to-noise ratio (SDNR), flow artifact-to-noise ratio (FNR), and geometric distortion were measured and/or calculated. Our results showed that to obtain high SNR, SDNR, and data acquisition efficiency while minimizing FNR and geometric distortion, the readout duration should be 10-15 msec at 1.5 T.

Mode of activation of salt secretion by C-type natriuretic peptide in the shark rectal gland.

We studied the modes of activation of the salt-secreting rectal gland of the spiny dogfish, Squalus acanthias, by the native cardiac peptide CNP. The stimulatory action of CNP in isolated perfused glands is inhibited by 10 mM procaine, presumably by blocking release of vasoactive intestinal peptide (VIP) from nerves. Procaine reduces the slope of the dose-response curve of human CNP and that of shark CNP (each P < 0.0001). CNP increases short-circuit current in cultured rectal gland cells from 4.8 +/- 1.6 to 27.0 +/- 7.8 microA/cm2. It also stimulates the secretion of chloride in isolated perfused glands in the presence of 10 mM procaine from 72 +/- 31 to 652 +/- 173 microeq. h(-1). g(-1). These results suggest that CNP has a direct cellular action not mediated by the neural release of VIP. The residual stimulation of perfused glands in the presence of procaine was almost completely inhibited by staurosporine [10 nM; an inhibitor of protein kinase C (PKC)] from 652 +/- 173 to 237 +/- 61 microeq. h(-1). g(-1). Although CNP stimulates guanylyl cyclase in shark rectal gland, chloride secretion of perfused glands was not elicited by 8-bromoadenosine-cGMP (8-BrcGMP) alone nor by the activator of PKC phorbol ester. The combination of PKC activation and 8-BrcGMP infusion, however, stimulated chloride secretion in perfused glands from 94 +/- 30 to 506 +/- 61 microeq. h(-1). g(-1), a level comparable to that observed in glands blocked with procaine. Several parallel pathways appear to be synergistic in activating chloride secretion stimulated by CNP in the rectal gland.

Visualization of aortic valve leaflets using black blood MRI.

Although magnetic resonance imaging (MRI) is capable of imaging various physiological parameters associated with the heart valves, it has generally been difficult to visualize the valve leaflets directly. The aortic valve was imaged in 120 patients referred for cardiac MRI to assess myocardial volumes or mass. The average patient age was 37 and ranged from 9 to 75 years. Heart rate ranged from 43 to 100 bpm. Imaging was performed on a 1.5 T scanner equipped with enhanced gradients and a cardiac phased-array coil. A double inversion recovery fast spin-echo sequence was used to acquire short-axis images of the aortic valve in a breath-hold (15 +/- 3 seconds). All three leaflets of the aortic valve were seen in 102 of 120 studies (85%). Two leaflets were detected in another 15 subjects. No leaflets were seen in three individuals. Seven cases of a bicuspid or thickened aortic valves were clearly distinguished from normal valves. The signal-to-noise ratio of aortic leaflets (14 +/- 5) was significantly higher than that of the residual blood signal in the aortic root (7 +/- 4, P < 0.001). MR images showed the aortic valve leaflets in a high fraction of people with suspected normal aortic valves and detected seven cases of abnormal aortic valves. The potential of MRI to study both the anatomic and functional consequences of valvular heart disease warrants further study. J. Magn. Reson. Imaging 1999;10:771-777.

Real-time cardiac MRI using DSP's.

A real-time cardiac magnetic resonance imaging (MRI) system has been implemented using digital signal processing (DSP) technology. The system enables real-time acquisition, processing, and display of ungated cardiac movies at moderate video rates of 20 images/s. A custom graphical user interface (GUI) provides interactive control of data acquisition parameters and image display functions. Images can be compressed into moving-picture experts group (MPEG) movies, but are displayed on the console without compression during the scan. Compared to existing real-time MRI systems, implementation with DSP's allows rapid parallel computations, fast data transfers, and greater system flexibility, including the ability to scale to multiple channels, at the expense of somewhat higher component cost.

Myocardial velocity gradient imaging by phase contrast MRI with application to regional function in myocardial ischemia.

Velocity-encoded phase contrast magnetic resonance imaging (MRI) has the potential to quantify regional myocardial contractile function with a sensitivity to motion comparable to implanted ultrasonic crystals. An MRI sequence and post-processing algorithm were developed to measure myocardial velocity gradients on a 1.5 T MRI scanner. These methods were validated on a rotating phantom and applied to dogs before (n = 11) and during prolonged coronary occlusion (n = 5). In phantom validation studies, the average absolute error corresponded to motion equivalent to 0.03 +/- 0.04 mm (mean +/- SD) during the repetition time of the experiment. Rigid body corrections during post-processing significantly simplified the interpretation of myocardial velocity vectors. In vivo, rigid body motion contributes substantially to the recorded myocardial velocities in systole and diastole and can give the false impression of regional wall motion abnormalities. After rigid body correction, normal systolic and diastolic velocity vectors in short-axis views of the left ventricle were primarily directed toward the center of the left ventricle. Transmural radial strain rate was 2.0 +/- 0.6 sec-1 during systole and -3.6 +/- 1.1 sec-1 during early diastole in normal canine hearts. Ischemic myocardium was easily discriminated from normal left ventricle by velocity-encoded phase contrast MRI both qualitatively and quantitatively (P < 0.01 in systole and P < 0.05 in early diastole). Although the myocardial velocity images have a spatial resolution on the order of a millimeter, the velocity encoding describes the mechanical consequences of focal myocardial ischemia with sensitivity to submillimeter displacement of the pixels. The three-dimensional nature of velocity-encoded MRI is particularly well suited to the study of the complex motion of the heart in vivo.

Evaluation of changes in intrarenal oxygenation in rats using multiple gradient-recalled echo (mGRE) sequence.

Changes in intrarenal oxygenation in rats during pharmacological stimuli were evaluated with a multiple gradient-recalled echo (mGRE) sequence. With administration of the loop diuretic furosemide, oxygenation in the medulla improved; acetazolamide, a proximal tubular diuretic, produced no significant change. These results are consistent with our previous studies in humans and resemble earlier studies of medullary oxygenation using oxygen microelectrodes in anesthetized rats. The technique may be useful in the evaluation of therapeutic strategies in animal models of pathophysiological states such as acute renal failure.