Isolated left ventricular apical hypoplasia: a new congenital anomaly described with cardiac tomography.

OBJECTIVE: To describe cardiac tomography findings of an apparently new, presumably congenital, left ventricular (LV) abnormality noted consistently in three patients. PATIENTS: Three patients presenting with non-specific symptoms including fatigue, shortness of breath, or chest discomfort were evaluated with cardiac tomography for cardiac structure and function. RESULTS: Findings from the three patients were very similar: a truncated and spherical LV with abnormal diastolic and systolic function, invagination of fatty material into the myocardium of the defective LV apex, origin of a complex papillary network in the anteroapical LV, and an elongated right ventricle wrapping around the deficient apex. CONCLUSIONS: Isolated LV apical hypoplasia is a unique, presumably congenital, cardiac anomaly that is an important condition to recognise.

Carotid MR angiography: phase II study of safety and efficacy for MS-325.

PURPOSE: To evaluate the safety and efficacy of MS-325 in patients suspected of having carotid arterial disease. MATERIALS AND METHODS: Fifty carotid arteries in 26 patients were imaged with three-dimensional spoiled gradient-recalled-echo magnetic resonance (MR) angiography at 5 and 50 minutes after injection of MS-325. MS-325 was administered intravenously as a single dose of 0.01, 0.03, or 0.05 mmol per kilogram of body weight as determined with a dose randomization scheme for four, nine, and 13 patients, respectively. Safety, including clinical laboratory changes and electrocardiographic monitoring, was assessed until approximately 3 days after injection. Conventional contrast agent-enhanced angiography was used as the standard of reference. Independent readers blinded to the dose interpreted the MR angiographic and conventional images. Images were assessed for location and extent of carotid arterial stenosis. RESULTS: There were no severe or serious adverse events. For the determination of clinically significant stenosis (>70%) on the 5-minute images, sensitivity, specificity, and accuracy (P =.07, three-way comparison) were 100%, 100%, and 100%; 63%, 100%, and 88%; and 40%, 75%, and 55% at 0.01, 0.03, and 0.05 mmol/kg, respectively. Sensitivity and specificity for images at 50 minutes after MS-325 administration showed the same trends as the 5-minute images. CONCLUSION: Overall accuracy for MS-325-enhanced carotid MR angiography performed during steady-state conditions of circulating contrast agent approximately 5 minutes after injection was high (88%-100%) at 0.03 and 0.01 mmol/kg. MS-325 was well tolerated at all evaluated doses.

The clinical value of ferric ammonium citrate: a positive oral contrast agent for T1-weighted MR imaging of the upper abdomen.

This study was undertaken to determine whether ferric ammonium citrate (FAC), a positive magnetic resonance (MR) contrast agent, is of clinical value in demonstrating or excluding pathology of the upper gastrointestinal tract. A retrospective review was performed of pre- and post-FAC studies of MR examinations in 203 patients from phase II and III clinical trials in whom final diagnoses had been established based on the results of biopsy, surgery, or independent imaging procedures. Two independent reviewers made randomized and blinded assessments of the stomach, duodenum, and pancreas. FAC significantly increased the certainty of diagnosis for normal studies of the stomach and duodenum for both readers (P < 0.001) and for abnormal studies of the stomach for one reader (P = 0.004). FAC also significantly increased the certainty of diagnosis for normal pancreas for one reader (P < 0.001). FAC significantly (P < 0.001) increased accuracy and specificity for diagnoses involving the stomach and duodenum for both readers and for one reader for the pancreas. There was significant improvement in sensitivity for gastric diagnoses (P = 0.013) for one reader but not for the duodenum or pancreas. We conclude that FAC is helpful in demonstrating and excluding upper gastrointestinal pathology on MR.

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging.

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.

Right transatrial approach to relieve pulmonary stenosis in patients with corrected transposition of the great vessels: a new operation without use of an extracardiac conduit.

BACKGROUND: A new operation to relieve pulmonary obstruction is proposed for patients with corrected transposition of the great vessels and pulmonary stenosis (PS). A right transatrial approach involves excising or detaching the right-sided atrioventricular valve (AV). Next, the pulmonary outflow tract is opened wide with an incision extending from the right-sided ventricle upward across the AV valve annulus. This incision extends into the main trunk of the pulmonary artery located behind the right atrium. A patch, with or without implantation of a pulmonary valve prosthesis, widens the outflow tract, thus avoiding use of an extracardiac conduit. METHOD: We describe this operation performed in a 51-year-old man who had previously undergone correction with an extracardiac conduit that had become obstructed. The patient had severe right-sided AV valve insufficiency and complete heart block with a functioning transvenous pacemaker. We replaced the right-sided AV valve and positioned the permanent pacemaker lead outside of the prosthetic skirt. The PS was corrected as described above and a pulmonary prosthetic valve implanted. Use of an extracardiac conduit was avoided altogether. CONCLUSION: This technique may be applicable even without excising the right-sided AV valve. The clinical result for our patient is still optimal 4 years after surgery.

Magnetic resonance first-pass myocardial perfusion imaging: clinical validation and future applications.

Clinical studies suggest that magnetic resonance first-pass (MRFP) perfusion imaging is comparable to current diagnostic tests that are used clinically for the assessment of myocardial perfusion. In addition, magnetic resonance imaging (MRI) perfusion imaging is a noninvasive method for determining myocardial blood flow. The spatial resolution (in-plane spatial resolution < 3 mm) is sufficient to differentiate between subendocardial perfusion and subepicardial perfusion. The measurement can be repeated regularly without any adverse effects for the patient. MRI perfusion measurements can be combined with the evaluation of global function and regional wall thickening. Currently, there is no other imaging technique that offers similar advantages. The MRI perfusion measurements can be carried out during baseline conditions and during maximal hyperemia induced with either adenosine or dipyridamole. The ratio of the measured myocardial blood flows provides an estimate of the absolute and relative myocardial perfusion reserve. The perfusion reserve determined with MRFP imaging is a quantitative measure for the assessment of the collateral-dependent myocardial flow. Based on the available data using MRFP perfusion imaging, the current clinical first-line perfusion imaging tests are going to be challenged in the near future. J. Magn. Reson. Imaging 1999;10:676-685.

Contrast enhanced body magnetic resonance angiography.

The use of gadolinium contrast for body MRA is reviewed. Considerations for timing of the bolus of contrast are discussed. The utility of this technique is illustrated through clinical examples. Contrast enhanced MRA is rapidly replacing conventional angiography for many applications.

Myocardial viability.

This article reviews various means to assess myocardial viability by imaging, and provides recommendations for current clinical practice. This article also discusses future directions in assessing myocardial viability.

Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase II clinical trial data.

The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide contrast agent, are presented. One hundred and four patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg. Overall, 15% patients reported a total of 33 adverse events, regardless of causality. The adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and rash (2.9%). No serious adverse events were reported during the 48 hour observation period. There were no clinically significant effects on vital signs, physical examination, and laboratory results. Ferumoxtran-10 is a safe and well tolerated MR contrast agent.

Direct comparison of an intravascular and an extracellular contrast agent for quantification of myocardial perfusion. Cardiac MRI Group.

A direct comparison of extracellular and intravascular contrast agents for the assessment of myocardial perfusion was carried out in a porcine model (N = 5) with a flow-limiting occluder on the left anterior descending coronary artery. Rapid imaging during the first pass of an extracellular or intravascular contrast agent with a saturation-recovery-prepared TurboFLASH sequence showed comparable peak contrast-to-noise enhancements in myocardial tissue regions with flows averaging 1.1 +/- 0.2 at baseline to 4.8 +/- 0.6 ml/min/g during hyperemia. The coefficient of variation between the MR estimates of blood flow with Gadomer-17 and the microsphere blood flow measurements was 11 +/- 11%, while the corresponding co-efficient of variation for blood flow estimates with the extracellular CA was 23 +/- 11%. Blood volume differences between rest and hyperemia observed with the intravascular tracer were significant (Vvasc(rest) = 0.078 +/- 0.013 ml/g, versus Vvasc(hyperemia) = 0.102 +/- 0.019 ml/g; p < 0.05). The effects of water exchange were minimized through the choice of pulse sequence parameters to provide blood volume estimates consistent with the changes expected between rest and hyperemia. This study represents the first application of multiple indicators in first pass imaging studies for the assessment of myocardial perfusion. The use of an intravascular instead of an extracellular contrast agent allows a reduction of the degrees of freedom for modeling tissue residue curves and results in improved accuracy of blood flow estimates.

Are critically ill older patients treated differently than similarly ill younger patients?

Our goal was to determine whether critically ill older patients are treated differently than middle-aged patients. If so, what factors besides age contribute to that difference? Internal medicine residents (n = 46) and practicing internists (n = 41) received 8 clinical vignettes of 4 critically ill 85-year-old patients and 4 critically ill 50-year-old patients. Each patient had a distinct premorbid mental and physical state. Each respondent selected from 4 levels of therapeutic aggressiveness for each patient. The main outcome measure was the proportion of physicians who intended to treat the older of each matched pair of patients less aggressively than the younger one (that is, downgraded for age). Eight physicians (9%) treated a previously unimpaired 85-year-old patient less aggressively than a comparable 50-year-old patient. When the matched patients were either premorbidly mentally or physically impaired (but not both), about 20% of physicians downgraded for age. Most downgraded for age in matched patients who were premorbidly both mentally and physically impaired. We conclude that age alone does not engender much therapeutic bias against older patients as long as they are physically and mentally intact before the onset of their acute illness. As premorbid disabilities multiply, older patients may be treated less aggressively than younger ones with similar impairments and clinical presentations.

Functional impact of an increase in ventricular mass after myocardial damage and its attenuation by converting enzyme inhibition.

BACKGROUND: A increase in left ventricular mass after ventricular damage has been identified as an initial response to injury. However, the functional significance of this response has not been clearly established and is the focus of this study. METHODS AND RESULTS: Twelve mongrel dogs underwent transmyocardial direct current shock to produce transmural left ventricular damage. Six were assigned to converting enzyme inhibitor therapy initiated 24 hours after damage and continued for 4 weeks. The remaining six dogs served as a control group. Left ventricular structure (mass and end diastolic volume) and systolic function (regional and global ejection fraction at rest and during afterload stress) were assessed by magnetic resonance imaging before damage and at the end of the 4-week period. After myocardial damage, left ventricular mass increased from 93.6 +/- 4.0 to 107.5 +/- 3.4 gm in the control group (P < .01) with no change in ventricular volume. Ramipril-treated dogs displayed a reduction in mass (83.2 +/- 2.2 to 74.6 +/- 2.9 gm, P < .05). In the control group, there was greater reduction in global ejection fraction in response to afterload stress at 4 weeks compared with baseline (-16 +/- 4 vs -4 +/- 3%, P = .03). Ejection fraction response to afterload stress was maintained at 4 weeks in the converting enzyme inhibitor-treated group (-5 +/- 3 vs - 1 +/- 4%) and was different at 4 weeks from the control group (-1 +/- 4 vs -16 +/- 4%, P = .004). CONCLUSION: The increase in left ventricular mass noted after direct current shock was associated with the impairment of systolic function during afterload stress. Inhibition of this mass increase results in preservation of function, thus further supporting the concept that attenuation of ventricular remodeling should be a therapeutic goal.

Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution.

The myocardial perfusion reserve, defined as the ratio of hyperemic and basal myocardial blood flow, is a useful indicator of the functional significance of a coronary artery lesion. Rapid magnetic resonance (MR) imaging for the noninvasive detection of a bolus-injected contrast agent as a MR tracer is applied to the measurement of regional tissue perfusion during rest and hyperemia, in patients with microvascular dysfunction. A Fermi function model for the distribution of tracer residence times in the myocardium is used to fit the MR signal curves. The myocardial perfusion reserve is calculated from the impulse response amplitudes for rest and hyperemia. The assumptions of the model are tested with Monte Carlo simulations, using a multiple path, axially distributed mathematical model of blood tissue exchange, which allows for systematic variation of blood flow, vascular volume, and capillary permeability. For a contrast-to-noise ratio of 6:1, and over a range of flows from 0.5 to 4.0 ml/min per g of tissue, the ratio of the impulse response amplitudes for hyperemic and basal flows is linearly proportional to the ratio of model blood flows, if the mean transit time of the input function is shorter than approximately 9 s. The uncertainty in the blood flow reserve estimates grows both at low (< 1.0 ml/min/g) and high (> 3-4 ml/min/g) flows. The predictions of the Monte Carlo simulations agree with the results of MR first pass studies in patients without significant coronary artery lesions and microvascular dysfunction, where the perfusion reserve in the territory of the left anterior descending coronary artery (LAD) correlates linearly with the intracoronary Doppler ultrasound flow reserve in the LAD (r = 0.84), in agreement with previous PET studies.

Proton MR spectroscopy and neuropsychological testing in adrenoleukodystrophy.

PURPOSE: To determine early signs of disease in patients with childhood-onset cerebral adrenoleukodystrophy (COCALD) with the use of proton MR spectroscopy. METHODS: Eleven children with posterior COCALD involvement and three children with anterior COCALD involvement were studied with single-voxel proton MR spectroscopy and neuropsychological testing. Findings were compared with those in five healthy control subjects. RESULTS: Areas of abnormal T2 signal intensity in children with COCALD showed abnormal metabolite ratios relative to those of control subjects as follows: decreased N-acetylaspartate (NAA)/Creatine (Cr) and NAA/Choline (Ch) and increased Ch/Cr. Metabolite ratios from normal-appearing brain regions in the same patients also were abnormal, with reduced NAA/Cr and NAA/Ch and increased Ch/Cr values. The mean metabolite ratios in normal-appearing regions were between those in the abnormal regions and those found in the control subjects. Statistical comparison of these ratios with neuropsychological test scores, which are specific for anterior and posterior brain functions, showed a significant correlation with the abnormal metabolite ratios. Our results indicate that the normal-appearing brain regions in these patients are metabolically abnormal. CONCLUSION: Proton MR spectroscopy could be a useful noninvasive tool to evaluate extent of disease in patients with COCALD.

Myocardial perfusion reserve: assessment with multisection, quantitative, first-pass MR imaging.

PURPOSE: To demonstrate the feasibility of determining myocardial blood flow changes and the myocardial perfusion reserve with magnetic resonance (MR) first-pass imaging, to validate the MR results by means of comparison with radiolabeled microsphere flow measurements in an animal model, and to compare the coronary flow reserve with the perfusion reserve at MR imaging in patients with hemodynamically nonsignificant coronary lesions and angina. MATERIALS AND METHODS: Arrhythmia-insensitive, first-pass, multisection, T1-weighted MR imaging with contrast agent enhancement was performed in eight pigs with acute ischemia and in eight adult patients (six women, two men). In the pigs, microsphere flow measurements were obtained in parallel with the MR measurements. In the patients, the coronary flow reserve was measured with an intracoronary Doppler flow ultrasound probe for comparison with the MR perfusion reserve. RESULTS: In the animal studies, there was linear correlation between MR perfusion indexes and the microsphere flow measurements (r = .88, P < .01). In the patients, the regional perfusion reserve matched the coronary flow reserve (linear regression with a slope of 1.02 +/- 0.09, r = .80). CONCLUSION: The myocardial perfusion reserve can be quantified with first-pass MR imaging. In patients with microvascular dysfunction, the myocardial perfusion reserve matches the reduced coronary flow reserve.