Gadolinium-enhanced magnetic resonance imaging in hypertrophic cardiomyopathy: in vivo imaging of the pathologic substrate for premature cardiac death?
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Biomedical subjects
Publications and source records attributed to Robert M Judd.
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BACKGROUND: Myocardial infarcts are routinely detected by nuclear imaging techniques such as single photon emission computed tomography (SPECT) myocardial perfusion imaging. A newly developed technique for infarct detection based on contrast-enhanced cardiovascular magnetic resonance (CMR) has higher spatial resolution than SPECT. We postulated that this technique would detect infarcts missed by SPECT. METHODS: We did contrast-enhanced CMR and SPECT examinations in 91 patients with suspected or known coronary artery disease. All CMR and SPECT images were scored, using a 14-segment model, for the presence, location, and spatial extent of infarction. To compare each imaging modality to a gold standard, we also acquired contrast-enhanced CMR and SPECT images in 12 dogs with, and three dogs without, myocardial infarction as defined by histochemical staining. FINDINGS: In animals, contrast-enhanced CMR and SPECT detected all segments with nearly transmural infarction (>75% transmural extent of the left-ventricular wall). CMR also identified 100 of the 109 segments (92%) with subendocardial infarction (<50% transmural extent of the left-ventricular wall), whereas SPECT identified only 31 (28%). SPECT and CMR showed high specificity for the detection of infarction (97% and 98%, respectively). In patients, all segments with nearly transmural infarction, as defined by contrast-enhanced CMR, were detected by SPECT. However, of the 181 segments with subendocardial infarction, 85 (47%) were not detected by SPECT. On a per patient basis, six (13%) individuals with subendocardial infarcts visible by CMR had no evidence of infarction by SPECT. INTERPRETATION: SPECT and CMR detect transmural myocardial infarcts at similar rates. However, CMR systematically detects subendocardial infarcts that are missed by SPECT.
CMR is a rapidly developing new modality with applications in clinical cardiology for detection and assessment of myocardial ischemia and viability. CMR perfusion results for the detection of ischemia in comparison with stress echocardiography and scintigraphic techniques are reasonable, but all the studies reported to date have been conduced in selected patients. Larger studies in patient populations reflecting a broader spectrum of disease are necessary before perfusion CMR can be envisaged as a clinically reliable and robust diagnostic tool. Other CMR techniques provide a variety of novel methods of obtaining information on postischemic viability. Signs of viability that can be observed by CMR are the absence of late gadolinium-based contrast enhancement in a myocardial region involved in a recent infarct, any sign of wall thickening at rest (which is detectable with high accuracy by CMR), wall thickening after stimulation by low-dose dobutamine, and preserved wall thickness. Conversely, myocardial necrosis is characterized by signal enhancement of the infarct area after injection of Gd-DTPA, reduced wall thickness in chronic infarcts, and absence of a contractile reserve during dobutamine stimulation. Dobutamine CMR and late enhancement contrast-enhanced CMR predict contractile improvement after revascularization.
Recently, numerous studies have demonstrated the effectiveness of a segmented inversion recovery fast gradient echo (seg IR-FGE) sequence for differentiating injured from normal myocardium. This technique for delayed enhancement imaging has been shown to be effective in identifying the presence and extent of myocardial infarction, as well as predicting improvement in contractile function after coronary revascularization. In this article we outline the procedure of delayed enhancement imaging performed at our center, describe the seg IR-FGE sequence in more detail, including our process for choosing sequence settings, review our process of image interpretation, and highlight potential pitfalls (and techniques to overcome them) that we have encountered in our experience with performing the technique in over 1500 patients.
Labeling stem cells with FDA-approved superparamagnetic iron oxide particles makes it possible to track cells in vivo with magnetic resonance imaging (MRI), but high intracellular levels of iron can cause free radical formation and cytotoxicity. We hypothesized that the use of cationic liposomes would increase labeling efficiency without toxic effects. Rabbit skeletal myoblasts were labeled with iron oxide by: 1) uptake of iron oxide incorporated into cationic transfection liposomes (group I) or 2) customary endocytosis (group II). In both groups, cell proliferation and differentiation were measured and toxicity was assayed using trypan blue and ratio fluorescence microscopy with BODIPY 581/591 C11. The effects of the intracellular iron oxide on magnetic resonance image intensities were assessed in vitro and in vivo. Both methods resulted in uptake of iron intracellularly, yielding contrast-inducing properties on MRI images. In group II, however, incubation with iron oxide at high concentrations required for endocytosis caused generation of free radicals, a decrease in proliferation, and cell death. Cytotoxic effects in the remaining cells were still visible 24 h after incubation. Conversely, in group I, sufficient intracellular uptake for detection in vivo by MRI could be achieved at 100-fold lower concentrations of iron oxide, which resulted in a high percentage of labeled cells, high retention of the label, and no cytotoxic effects even after stressing the cells with a hypoxia-reoxygenation insult. The use of cationic liposomes for iron oxide stem cell labeling increases labeling efficiency approximately 100-fold without toxic effects. This technique results in high-contrast-inducing properties on MRI images both in vitro and in vivo and could thus be a valuable tool for tracking stem cells noninvasively.
OBJECTIVES: We sought to ascertain whether myocardial scarring occurs in living unselected patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Myocardial scarring is known to occur in select HCM patients, who were highly symptomatic prior to death or who died suddenly. The majority of HCM patients, however, are minimally symptomatic and have not suffered sudden death. METHODS: Cine and gadolinium-enhanced magnetic resonance imaging was performed in 21 HCM patients who were predominantly asymptomatic. Gadolinium hyperenhancement was assumed to represent myocardial scar, and the extent of scar was compared to left ventricular (LV) morphology and function. RESULTS: Scarring was present in 17 patients (81%). Scarring occurred only in hypertrophied regions (> or =10 mm), was patchy with multiple foci, and predominantly involved the middle third of the ventricular wall. All 17 patients had scarring at the junction of the interventricular septum and the right ventricular (RV) free wall. On a regional basis, the extent of scarring correlated positively with wall thickness (r = 0.36, p < 0.0001), and inversely with wall thickening (r = -0.21, p < 0.0001). On a per patient basis, the extent of scarring (mean, 8 +/- 9% of LV mass) was minimally related to maximum wall thickness (r = 0.40, p = 0.07) and LV mass (r = 0.33, p = 0.15), and correlated inversely with ejection fraction (r = -0.46, p = 0.04). CONCLUSIONS: Myocardial scarring is common in asymptomatic or mildly symptomatic HCM patients who have not suffered sudden death. When present, scarring occurs in hypertrophied regions, is consistently localized to the junctions of the septum and RV free wall, and correlates positively with regional hypertrophy and inversely with regional contraction.
BACKGROUND: The reproducibility of contrast-enhanced MRI has not been established. We compared MRI reproducibility for infarct size determination with that of (99m)Tc-sestamibi (MIBI) single photon emission computed tomography (SPECT). METHODS AND RESULTS: Patients with chronic myocardial infarction defined by enzymes (peak creatine kinase-MB 173+/-119 U/L) were scanned twice by MRI (MRI I and MRI II, n=20) and twice by SPECT (SPECT I and SPECT II, n=15) on the same day. The MRI contrast agent was injected during MRI I but not MRI II to test the effect of imaging time after contrast. Resting Tc-MIBI SPECT images were acquired and infarct size was determined with commercial software. Infarct size in patients scanned by MRI and SPECT was 14+/-6% of left ventricular mass (%LV) by MRI (range 4%LV to 27%LV) and 14+/-7%LV by SPECT (range 4%LV to 26%LV). MRI I and II scans were performed 10+/-2 and 27+/-3 minutes after contrast, respectively. For MRI, the difference in infarct size between scans I and II (bias) was -0.1%LV, and the coefficient of repeatability was +/-2.4%LV. For SPECT, bias was -1.3%LV, and the coefficient of repeatability was +/-4.0%LV. Within individual patients, no systematic differences in infarct size were detected when the 2 MRI scans were compared, the 2 SPECT scans were compared, or MRI was compared to SPECT. CONCLUSION: The size of healed infarcts measured by contrast-enhanced MRI does not change between 10 and 30 minutes after contrast. The clinical reproducibility of contrast-enhanced MRI for infarct size determination compares favorably with that of routine clinical SPECT.
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BACKGROUND: Discrepant reports have been published recently regarding the relationship of contrast-enhanced magnetic resonance image intensities to reversible and irreversible ischemic injury. Unlike image intensities, contrast agent concentrations provide data independent of the MRI technique. We used electron probe x-ray microanalysis (EPXMA) to simultaneously examine concentrations of Gd, Na, P, S, Cl, K, and Ca over a range of myocardial injuries. Methods and Results- Reversible and irreversible injury were studied in 38 rabbits divided into 4 groups defined by occlusion and reperfusion time, as well as time the animals were euthanized. Gd-DTPA was administered, and the hearts were excised and rapidly frozen, cryosectioned, freeze-dried, and examined by EPXMA in up to 3 regions: remote, infarcted, and at risk but not infarcted. Infarcted regions were defined by anti-myoglobin antibody or triphenyltetrazolium chloride staining. Regions at risk were defined by fluorescent microparticles administered during occlusion. Compared with remote regions, in acutely infarcted regions, Gd was increased (235+/-24%, P<0.005) in the same 50 x 100-microm areas in which Na was increased (154+/-5%, P<0.001) and K was decreased (52+/-8%, P<0.001). Similarly, in chronically infarcted regions, Gd was increased (472+/-78%, P<0.001) in areas in which Na was increased (332+/-28%, P<0.001) and K was decreased (47+/-5%, P<0.001). Also compared with remote regions, however, concentrations of Gd, Na, and K were not elevated after reperfusion in regions that were at risk but not infarcted (P=NS). CONCLUSIONS: Regional elevations in myocardial MRI contrast agent concentrations are exclusively associated with irreversible ischemic injury defined histologically and by regional electrolyte concentrations.
PURPOSE: To test the accuracy of a high performance true fast imaging with steady-state precession (TrueFISP) pulse sequence for the assessment of left ventricular (LV) mass in a large animal model on 1.5-T scanners. MATERIALS AND METHODS: We imaged dogs (N = 10) on a clinical 1.5-T clinical scanner using electrocardiogram (ECG)-gated TrueFISP. In all animals, contiguous segmented k-space cine images were acquired from base to apex (in-plane resolution 1 x 1 mm(2), slice thickness 5 mm, TR = 4.8 msec, TE = 1.6 msec) during repeated breath-holds. In nine of the 10 animals, single-shot images gated to end-diastole were also acquired from base to apex in a single breath-hold (in-plane resolution 1 x 1 mm(2), slice thickness 5 mm, TR = 3.2 msec, TE = 1.6 msec). After imaging, animals were killed, the left ventricle was isolated, and the true mass of the left ventricle (free wall and septum) was determined. Independently, two observers blinded to the post-mortem results computed LV masses based on analysis of the magnetic resonance (MR) images. RESULTS: Comparison of the computed LV mass using TrueFISP to the actual mass showed excellent agreement. Cine-systole was the most accurate technique (mass = 98.6% +/- 4.5% actual, bias = 1.2 +/- 3.4 g) followed by cine-diastole (mass = 97.9% +/- 5.3% actual, bias = 1.8 +/- 4.1 g) and single shot (mass = 94.7% +/- 7.9% actual, bias = 4.2 +/- 6.3 g). Inter- and intra-observer variabilities were low (5.8% +/- 7.1% and 0.4% +/- 4.8%, respectively). CONCLUSION: We conclude that TrueFISP imaging is an accurate, rapid method to determine ventricular mass. In single-shot mode, TrueFISP requires only one breath-hold to estimate the mass of the heart within 6% of the actual value, whereas the segmented k-space implementation measured LV mass to within 3% of the true value.
A fast imaging method is described that yields an approximately six-fold acquisition time reduction relative to conventional techniques. The method involves: 1) acquisition of every sixth k-space line; 2) shifting of acquired k-space lines between odd and even frames; and 3) a single-frame correction image. Reconstruction is achieved by temporal interpolation for k-space lines not acquired combined with subtraction of stationary fold-in artifacts. Seven patients with heart disease and one volunteer were evaluated. SNR was measured in myocardium and the ventricular cavity for both the conventional and new technique. The method is best suited for fast imaging of moving objects confined to a small region within a larger stationary object, such as the heart within the thoracic cavity. It can be implemented in cine and functional imaging sequences and, in principle, in perfusion sequences.