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Comparing dichotomous screening tests when individuals negative on both tests are not verified.

Two dichotomous screening tests are often compared by performing both tests in a sampled population, and submitting positive results on either test to verification by the reference standard. Unbiased estimates of the true positive and false positive rates of each test cannot be estimated directly. However, unbiased estimates of the relative true positive and relative false positive rates may be obtained. When one test has a higher true positive rate at the expense of a higher false positive rate, the trade-off is represented by the ratio of extra false positives detected to extra true positives detected. A 95% confidence interval for this ratio is derived. This ratio is prevalence dependent and only applies to the sampled population. For target populations of different prevalence, estimates of the ratio may be obtained if one of the following applies: (i) the test characteristics of one test are known; (ii) the relative prevalence is known; and (iii) certain assumptions are made.

Data Interpretation, Statistical↗

Quantification of human H1 histamine receptor mRNA from peripheral blood.

STUDY OBJECTIVE: To develop a reverse transcription (RT)-polymerase chain reaction (PCR) technique to detect and quantify human histamine1 (H1) receptor mRNA in peripheral blood. METHODS: Primer pairs were based on the human H1 receptor nucleotide sequence. A competitive reference standard (CRS) was developed that used the same primers as wild-type mRNA but contained a 92-bp deletion. RT-PCR was performed with 5 microg of total RNA obtained from venous blood of six subjects that was added to known concentrations of CRS RNA. Linear regression comparing wild-type with CRS product was used to quantify wild-type mRNA. MEASUREMENTS AND MAIN RESULTS: Three subjects had detectable H1 mRNA, with a range of 31-435 pg. In three subjects PCR product was not detected, although the presence of RNA was confirmed. Redesigned primer pairs showed mRNA to H1 receptor in two of the remaining subjects, but it was undetectable in the third. CONCLUSION: RT-PCR can be used to detect and quantify human H1 receptor mRNA from peripheral blood.

Adult↗

Gas chromatographic/mass spectrometric assay for profiling the enantiomers of 3,4-methylenedioxymethamphetamine and its chiral metabolites using positive chemical ionization ion trap mass spectrometry.

A qualitative GC/MS profile was obtained and its mass spectrometric features characterized for the analysis of the enantiomers of (RS)-3,4-methylenedioxymethamphetamine (MDMA) and its metabolites (RS)-3,4-methylenedioxyamphetamine (MDA), (RS)-4-hydroxy-3-methoxymethamphetamine (HMMA) and (RS)-4-hydroxy-3-methoxyamphetamine (HMA). A chiral derivatization method was selected to obtain the diastereomers required for the separation of the respective enantiomers with a non-chiral GC stationary phase. The selected derivatization consisted of a reaction with N-heptafluorobutyryl-(S)-prolyl chloride combined with a consecutive reaction with N-methyl-N-trimethylsilyltrifluoroacetamide, resulting in N-[heptafluorobutyryl-(S)-prolyl]-O-trimethylsilyl derivatives. Detection was carried out with electron ionization and positive chemical ionization (PCI) ion trap mass spectrometry. Mass spectra of the derivatives of reference standards of the compounds of interest obtained with PCI demonstrated that this method simultaneously induces proton and charge-transfer reactions in the ion trap. The advantage is that high mass information is provided while some fragmentation remains to elucidate structural details. Subsequently, in three urine samples obtained from different and unrelated MDMA intoxications, the enantiomers of MDMA and MDA were identified. In some urine samples also HMMA and/or HMA were found. In addition to these compounds, an unexpected compound and/or additional chiral metabolite, N-hydroxy-(RS)-3,4-methylenedioxyamphetamine, was identified in two out of three urine samples. Preliminary results also indicated an enantioselective metabolism in the N-demethylation pathway for MDMA in humans.

Biotransformation↗

Local effects of mifepristone on the nonhuman primate endometrium.

OBJECTIVE: To determine the effects of a low-dose mifepristone regimen on endometrium in the rhesus monkey by endometrial staging and analysis of molecular markers of endometrial receptivity. DESIGN: A prospective, randomized comparative study. SETTING: Academic research environment. ANIMAL(S): Normally cycling rhesus (Macaca mulatta) monkeys. INTERVENTION(S): Monkeys (5 per control or treatment group) received 0.03 mg of mifepristone in vehicle (sesame oil) per kilogram of body weight or vehicle daily from day 2 of the menstrual cycle to 7 days after the midcycle E2 surge. MAIN OUTCOME MEASURE(S): Serum estradiol (E2) and progesterone (P) levels; endometrial staging and immunoreactivity of leukemia inhibitory factor and interleukin-6 performed on fixed endometrial tissues; and relative abundance of endometrial estrogen and P receptor mRNA evaluated with semiquantitative reverse transcriptase polymerase chain reaction in which cyclophilin mRNA, a housekeeping gene product, was coamplified as the reference standard. RESULT(S): Mifepristone at 0.03 mg/kg/d induced a delay in the endometrial cycle with a shift from the late to midsecretory phase. This treatment regimen did not suppress the midcycle gonadotropin surge or, presumably, ovulation because P levels were normal during the midluteal phase. The staining intensity of leukemia inhibitory factor and interleukin-6 was dependent upon the endometrial stage and was decreased in treated monkeys. E and P receptor mRNAs increased significantly with mifepristone treatment compared with controls, another indication of delayed uterine staging. CONCLUSION(S): Mifepristone at 0.03 mg/kg/d had no antiovulatory effect but delayed development of the endometrium from the late to midsecretory phase. This study provides further evidence that endometrial maturation can be altered without affecting ovarian cyclicity.

Abortifacient Agents, Steroidal↗

Inaccuracies in digoxin measurement.

Six commercial digoxin immunoassay kits were evaluated for their accuracy of calibration and their extent of interference by digoxin-like immunoreactive substance (DLIS). Calibration accuracy was investigated with digoxin reference standards in pooled human serum. The Abbott and Becton Dickinson kits underestimate while the other kits overestimate digoxin concentration. The magnitude of this bias generally increases with increasing concentration of digoxin. Sera from digoxin-free patient populations with potential DLIS interference--pregnant women, newborns, hypertensives, and uremics--were analyzed with each kit. Healthy subjects not on digoxin therapy served as controls. Groups with DLIS interference, as exemplified by a significant difference of p less than 0.05 from controls, are: Abbott--newborns and pregnant women; Becton Dickinson--newborns and pregnant women; Dade--no difference; Dupont--newborns, uremics, pregnant women, and hypertensives; Kallestad--newborns; and Syva--newborns. The limitations of each individual digoxin method should be realized for DLIS interference and bias, and patient results from that method should be interpreted accordingly.

Adult↗

New immunoassay for the detection of Helicobacter pylori infection compared with urease test, 13C breath test and histology: validation in the primary care setting.

Helicobacter pylori plays a major role in peptic ulcer disease and, as a result, testing for H. pylori infection among patients with dyspepsia has often been advocated. The aim of the study was to determine the diagnostic accuracy, the analytical performance, and optimal cut-off point of a new serological assay, the Pyloriset EIA-G III for the detection of H. pylori infection in the primary care setting. For 113 primary care patients with dyspepsia urea breath test, CLO test, histology and serology tests were performed. Diagnostic accuracy of the Pyloriset EIA-G III was evaluated against a reference standard of a carbon urea breath test (CUBT), CLO test and histology (from gastric biopsies). Precision, linearity and correlation of the serological assay with the CUBT and former Pyloriset were also determined. At the optimal cut-off level of 40 U/ml, the positive predictive value was 92.1%, negative predictive value 96.3%, sensitivity 87.5%, and specificity 93.9%. The within-run precision was high. The recovery data were good. The correlation of both CUBT and the former Pyloriset EIA-G and the Pyloriset EIA-G III was high. At the cut-off level of 40 U/ml, the new Pyloriset EIA-G III is a reliable method to detect H. pylori infection in the primary care setting.

Adult↗

MR imaging appearance of fetal cerebral ventricular morphology.

PURPOSE: To elucidate further the magnetic resonance (MR) imaging appearance of fetal cerebral ventricles by comparing ultrasonographic (US) and MR images. MATERIALS AND METHODS: A retrospective review of MR and US images was performed for 110 normal fetuses and 94 fetuses with central nervous system abnormalities to assess lateral ventricular morphology as having (a) a normal appearance, (b) mild, disproportionate dilatation of the occipital horns with overall preservation of ventricular morphology, (c) colpocephaly with or without normal orientation of the frontal horns, (d) abnormal orientation of the frontal horns without colpocephaly, (e) an angular appearance, (f) fused frontal horns, (g) global dilation, or (h) a distorted appearance. Ventricular morphology on US and MR images was compared and correlated with reference standard diagnoses. RESULTS: US and MR imaging classifications were concordant in 145 of 188 (77%) examinations. Mild disproportion of occipital horns with respect to frontal horns was seen only on MR images. This ventricular configuration was present in eight of 110 normal fetuses and in 10 of 16 fetuses with isolated mild ventriculomegaly (P <.001). An angular configuration of the lateral ventricles, which is seen in fetuses with neural tube defects (NTDs), was present on review of MR images in 11 fetuses and on US images in one fetus. The ventricles of fetuses with NTDs and angular ventricles (3-12 mm) were significantly smaller than those of fetuses with NTDs and global dilatation of the ventricles (13-25 mm; P <.05). CONCLUSION: Ventricular contours differ with differing diagnoses of central nervous system abnormalities.

Brain Mapping↗

Tumor measurement in the nude mouse.

In this study, the pitfalls of tumor measurement in the nude mouse were evaluated. Regarding intermethod variation, diameters of subcutaneous tumors in nude mice were expressed as length, area, and volume; tumor weights were also recorded. These measurements were all compared to a reference standard: water displacement volume. Estimates of area and volume derived from caliper measurements correlated well with water displacement volume (r = 0.97 and 0.98, respectively). At necropsy, tumor weight was the most consistent and reproducible reflection of tumor volume (r = 1.0000). Regarding interobserver variation, mean absolute difference among volumes determined by several investigators who measured the same tumors in living animals was determined. This averaged 15% of the mean calculated volume. Regarding intraobserver variation, observers measured four separate masses in nude mice eight times each. The observers were prevented from realizing that the same animals were being repeatedly evaluated. Volumes were compared in order to quantify the average variation that occurs when a single investigator repeatedly measures the same mass. When large masses were measured, this error was 7%; when small masses were measured, the error was 27%. Recommendations are made for future work employing tumor measurement.

Animals↗

Quantification of recombinant human parathyroid hormone (rhPTH(1-84)) in human plasma by immunoassay: commercial kit evaluation and validation to support pharmacokinetic studies.

Immunoassays utilizing commercial kits designed for diagnostic use can be adapted and validated to meet Good Laboratory Practice (GLP) requirements to support pharmacokinetic (PK) studies. We illustrate in this paper a systematic approach for commercial kit evaluation and GLP-compliant method validation to establish selectivity, sensitivity, linearity, accuracy, precision and stability. Immunoassay kits for human parathyroid hormone (hPTH) quantification from three different vendors were assessed in a side-by-side comparison for their suitability for the PK analysis of recombinant humanPTH (rhPTH) in EDTA plasma. Two immunoradiometric (IRMA) assay kits and one immunoluminometric assay (ILMA) kit were evaluated. Since PTH is present as an endogenous component of human plasma, QC preparation in the biological matrix was handled differently than for a xenobiotic drug compound. The endogenous concentration of PTH was determined in plasma samples from 32 individual lots using the three kits. The lots with the lowest endogenous concentrations of PTH were selected, pooled to form the low QC and spiked with rhPTH to prepare the mid and high QCs. Four evaluation batches were run with each of the three commercial kits to evaluate reference standard linearity, and QC accuracy and precision. Selectivity against PTH peptide fragments PTH(7-84) and PTH(3-84) were assessed by cross-reactivity and accurate spike-recovery to the QC samples at two concentrations. One of the kits was chosen for full method validation because it had the lowest cross-reactivity against hPTH fragments (3-84) and (7-84), a wider dynamic range and the least total error. The accuracy and precision from six validation batches of the QCs were <or=8.1% C.V. and <or=7.9% R.E., respectively. Method robustness was shown by acceptable QC performance using a different batch of capture antibodies, through 12 batches of iodinated detection antibodies, and by the use of four analysts over 2 years of patient sample analysis from clinical trials.

Drug Stability↗

Gadolinium-enhanced breathhold three-dimensional time-of-flight renal MR angiography in the evaluation of potential renal donors.

PURPOSE: To evaluate the utility of gadolinium-enhanced three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) of the renal arteries in the evaluation of potential renal donors. MATERIALS AND METHODS: Fifty consecutive patients underwent gadolinium-enhanced 3D-TOF MRA of the renal arteries as part of their evaluation as possible renal donors. All imaging was performed on a 1.5-T system with use of a torso phased-array coil. Conventional T1-weighted axial spin-echo and T2-weighted axial fast spin-echo imaging was performed to evaluate the renal parenchyma. Coronal dynamic MRA was performed during bolus injection of 40 mL of gadolinium with use of a 3D-TOF sequence requiring a breathhold of approximately 30 seconds. Maximum-intensity-projection reconstructions were obtained of the renal arterial and venous anatomy. All studies were prospectively evaluated by a single radiologist experienced with body MRA. Intraoperative findings were used as the reference standard in 35 patients. To evaluate interobserver variability, each examination was evaluated for image quality, renal artery number, and anatomy by two radiologists experienced with MRA and blinded to the other's interpretations and surgical results. RESULTS: Ninety-eight percent of all MRAs were graded as diagnostic quality (Kappa value = 0.38; P < .05). Multiple renal arteries were identified in 29 (29%) of 100 kidneys. Four of 50 patients studied (8%) had renal parenchymal abnormalities identified with MR imaging. Sensitivity and specificity for accessory renal artery detection was 71% and 95%, respectively. Overall, accuracy for MRA in determining renal artery number was 90%. CONCLUSION: Gadolinium-enhanced breathhold 3D-TOF renal MRA is sufficient to assess the renal arteries in potential donors.

Adult↗

Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging.

BACKGROUND: Current imaging modalities, such as contrast angiography, accurately determine the degree of luminal narrowing but provide no direct information on plaque size. Magnetic resonance imaging (MRI), however, has potential for noninvasively determining arterial wall area (WA). This study was conducted to determine the accuracy of in vivo MRI for measuring the cross-sectional maximum wall area (MaxWA) of atherosclerotic carotid arteries in a group of patients undergoing carotid endarterectomy. METHODS AND RESULTS: Fourteen patients scheduled for carotid endarterectomy underwent preoperative carotid MRI using a custom-made phased-array coil. The plaques were excised en bloc and scanned using similar imaging parameters. MaxWA measurements from the ex vivo MRI were used as the reference standard and compared with MaxWA measurements from the corresponding in vivo MR study. Agreement between the in vivo and ex vivo measurement was analyzed using the Bland-Altman method. The paired in vivo and ex vivo MaxWA measurements strongly agreed: the mean difference (in vivo minus ex vivo) in MaxWA was 13.1+/-6.5 mm2 for T1-weighted (T1W) imaging (mean MaxWA in vivo=94.7 mm2, ex vivo=81.6 mm2) and 14.1+/-11.7 mm2 for proton density-weighted (PDW) imaging (mean MaxWA in vivo=93.4 mm2, ex vivo=79.3 mm2). Intraobserver and interobserver variability was small, with intraclass correlation coefficients ranging from 0.90 to 0.98. CONCLUSIONS: MRI is highly accurate for in vivo measurement of artery WA in atherosclerotic carotid lesions. This imaging technique has potential application monitoring lesion size in studies examining plaque progression and/or regression.

Arteriosclerosis↗

The Hospital Anxiety and Depression Rating Scale: a cross-sectional study of psychometrics and case finding abilities in general practice.

BACKGROUND: General practitioners' (GPs) diagnostic skills lead to underidentification of generalized anxiety disorders (GAD) and major depressive episodes (MDE). Supplement of brief questionnaires could improve the diagnostic accuracy of GPs for these common mental disorders. The aims of this study were to examine the usefulness of The Hospital Anxiety and Depression Rating Scale (HADS) for GPs by: 1) Examining its psychometrics in the GPs' setting; 2) Testing its case-finding properties compared to patient-rated GAD and MDE (DSM-IV); and 3) Comparing its case finding abilities to that of the GPs using Clinical Global Impression-Severity (CGI-S) rating. METHODS: In a cross-sectional survey study 1,781 patients in three consecutive days in September 2001 attended 141 GPs geographically spread in Norway. Sensitivity, specificity, optimal cut off score, and Area under the curve (AUC) for the HADS and the CGI-S were calculated with Generalized Anxiety Questionnaire (GAS-Q) as reference standard for GAD, and Depression Screening Questionnaire (DSQ) for MDE. RESULTS: The HADS-A had optimal cut off > or =8 (sensitivity 0.89, specificity 0.75), AUC 0.88 and 76% of patients were correctly classified in relation to GAD. The HADS-D had by optimal cut off > or =8 (sensitivity 0.80 and specificity 0.88) AUC 0.93 and 87% of the patients were correctly classified in relation to MDE. Proportions of the total correctly classified at the CGI-S optimal cut-off > or =3 were 83% of patients for GAD and 81% for MDE. CONCLUSION: The results indicate that addition of the patients' HADS scores to GPs' information could improve their diagnostic accuracy of GAD and MDE.

Adult↗

Adenocarcinoma involving the uterine cervix: magnetic resonance imaging findings in tumours of endometrial, compared with cervical, origin.

PURPOSE: To determine the distinctive magnetic resonance imaging (MRI) features of cervical and endometrial adenocarcinoma that present clinically as a cervical mass. MATERIALS AND METHODS: From 1999 to 2002, 56 patients with adenocarcinoma on the initial biopsy of a cervical mass underwent MRI at our institution. Of these, 42 had a visible mass on MRI. Pathology review of all available tissue was the reference standard. A site of origin was determined by the pathologist in 38 of the 42 patients, and these were the cases evaluated; of these patients, 32 cases had adenocarcinoma and 6 had adenosquamous cancers. RESULTS: Findings were significantly more prevalent in patients with adenocarcinomas of endometrial, compared with cervical, origin for endometrial thickening (11 [73%] and 3 [13%], respectively; P = 0.0003), endometrial mass (11 [73%] and 1 [4%], respectively; P < 0.0001), endometrial cavity expansion by a mass (9 [60%] and 2 [9%], respectively; P = 0.001), and invasion of myometrium from endometrium (9 [60%] and 0, respectively; P < 0.0001). CONCLUSION: Adenocarcinomas of the endometrium that involve the cervix have MRI features that help distinguish them from primary adenocarcinomas of the cervix.

Adenocarcinoma↗

Diagnostic management of venous thromboembolism.

The accuracy of diagnostic methods for the diagnosis of deep vein thrombosis and pulmonary embolism in symptomatic patients is critically reviewed. In addition, the safety of withholding anticoagulant therapy from patients with suspected deep vein thrombosis or pulmonary embolism in whom the qualified diagnostic strategy was normal is evaluated by determining the frequency of venous thromboembolic complications during 3 months of follow-up. It is shown that the currently used available diagnostic techniques for deep vein thrombosis are all able to identify the majority of patients who indeed have venous thrombosis. However, as result of its accuracy and practical advantages, compression ultrasound is the test of choice in the evaluation of symptomatic patients. Patients with a normal test outcome should be re-tested to detect the small proportion of patients with proximally extending calf vein thrombosis. In the strategy of repeated diagnostic testing, impedance plethysmography could be used as an alternative to ultrasonography. To obtain a reduction in repeat tests various diagnostic strategies have been evaluated and it was shown that these strategies, using non-invasive tests, can be as accurate and safe as the invasive reference strategy. The safeties of the various strategies were very similar; however, important differences were observed with respect to the practical implementation of the various diagnostic strategies. Simplification of the repeated testing strategy by using a D-dimer assay and/or a clinical decision rule seems to be promising. The reference standard for the diagnosis of pulmonary embolism remains pulmonary angiography. Several strategies based on non-invasive diagnostic methods have been evaluated for their safety and complexability. Perfusion-ventilation lung scanning is the most thoroughly evaluated non-invasive technique so far. It seems safe to withhold anticoagulant therapy in patients suspected of pulmonary embolism with a normal perfusion lung scan result; however, further testing is needed in the case of a non-diagnostic perfusion-ventilation lung scan result. At this moment angiography is the method of choice in this category of patients. D-dimer assays, clinical decision rules and ultrasound examinations of the legs seem to have a high potential to limit the need for angiography. Also, spiral computerized tomography and magnetic resonance imaging are promising techniques, but their role in the diagnostic management of pulmonary embolism is still uncertain.

Diagnostic Techniques and Procedures↗

Accuracy and reliability of remote retinopathy of prematurity diagnosis.

OBJECTIVE: To determine the accuracy and reliability of retinopathy of prematurity (ROP) diagnosis using remote review of digital images by 3 masked ophthalmologist readers. METHODS: An atlas was compiled of 410 retinal photographs from 163 eyes of 64 low-birth-weight infants taken using a wide-angle digital fundus camera. All the images were independently reviewed by 3 readers, and the diagnosis in each eye was classified into 1 of 4 ordinal categories: no ROP, mild ROP, type 2 prethreshold ROP, or ROP requiring treatment. Findings were compared with a reference standard of dilated indirect ophthalmoscopy with scleral depression performed by an experienced pediatric ophthalmologist. RESULTS: Sensitivities/specificities of the diagnosis of any ROP were 0.845/0.910 for the first reader, 0.816/0.955 for the second reader, and 0.864/0.493 for the third reader. Sensitivities/specificities of the diagnosis of ROP requiring treatment were 0.850/0.960 for the first reader, 0.850/0.973 for the second reader, and 0.900/0.953 for the third reader. When ROP was classified into ordinal categories, the overall weighted kappa for interreader reliability was 0.743. Intrareader reliability for detection of low-risk prethreshold ROP or worse was 100% for all readers. CONCLUSION: The accuracy, interreader reliability, and intrareader reliability of remote diagnosis of clinically relevant ROP based on digital imaging are substantial.

Birth Weight↗

Evaluation of the antipyretic effect of ketorolac, acetaminophen, and placebo in endotoxin-induced fever.

The authors studied the antipyretic effect of three intramuscular doses of ketorolac (15, 30, and 60 mg), acetaminophen 650 mg PO, and placebo in healthy male volunteers using an endotoxin-induced fever model. In this double-blind, double-dummy, parallel study, subjects were assigned randomly with equal probability to one of the above treatment groups. Thirty minutes after study medication administration, a 20 unit per kilogram dose of reference standard endotoxin (RSE) was administered intravenously, and temperature was determined every 15 minutes for an 8-hour period. Compared with placebo, all active treatment groups demonstrated a statistically significant reduction in both adjusted area under the temperature-by-time curve (AAUC) and the maximum increase over baseline temperature (dTmax). Furthermore, the 30 mg intramuscular dose of ketorolac demonstrated approximately the same antipyretic activity as the 650 mg oral dose of acetaminophen, and there was a statistically significant dose response across the three ketorolac doses studied (P < .0001). The majority of side effects reported during this study were symptoms associated with fever, including chills, headache, myalgia, and dizziness, all of which are effects of RSE. The frequency of side effects tended to be less in the treatment groups with the greatest antipyretic activity.

Acetaminophen↗

Variable-region subgroup distribution among lambda-type immunoglobulins in normal human serum.

The distribution of the major VL subgroups (V lambda I, V lambda II, V lambda III, V lambda IV, V lambda VI, and V lambda VIII) among lambda-type immunoglobulins (Igs) in normal serum was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) using a panel of murine anti-human V lambda-subgroup-specific monoclonal antibodies (MoAbs) and appropriate reference standard proteins. The mean concentration of lambda I, lambda II, lambda III, lambda IV, lambda VI, and lambda VIII Igs in serum specimens obtained from 23 adults was 2158, 162, 1958, 264, 225, and 169 micrograms/mL and represented 44, 3, 40, 5, 5, and 3% of the total Ig lambda population, respectively. The low percentage of lambda II Igs in normal serum was in marked contrast to the approximately 40% incidence of this V lambda subgroup found among lambda-type Bence Jones proteins and monoclonal serum Igs obtained from patients with multiple myeloma and AL amyloidosis, or approximately 60% in Waldenström's macroglobulinemia. The non-random expression of the V lambda II subgroup in these diseases implies a relationship between V lambda-gene usage and plasma cell, as well as certain types of lymphocytic dyscrasias.

Adult↗

Differentiating acute myocardial infarction from myocarditis: diagnostic value of early- and delayed-perfusion cardiac MR imaging.

PURPOSE: To prospectively determine whether early first-pass perfusion and delayed-enhancement magnetic resonance (MR) imaging sequences can enable differentiation of acute myocardial infarction (AMI) from myocarditis in patients with acute chest pain. MATERIALS AND METHODS: All examinations were performed according to guidelines of the institutional board on medical ethics and clinical investigation and after informed patient consent was obtained. Fifty-five patients with a clinical presentation suggestive but not typical of AMI were examined. At final diagnosis, 31 patients had AMI and 24 had myocarditis. At-rest MR imaging was performed and included first-pass perfusion and delayed-enhancement sequences. Three independent observers read each image data set separately and then in consensus. The main abnormalities included first-pass perfusion defects and delayed highly enhancing areas. The numbers and distributions of involved segments and the transmural extents and the shapes of the highly enhancing areas were noted. For comparisons between the AMI and myocarditis patient groups, the chi2 test was used to assess the locations of the abnormalities and the Mann-Whitney U test was used to assess the numbers of involved segments. The final diagnoses were obtained with coronary angiography as the reference standard for the AMI group and on the basis of normal coronary angiographic findings and the spontaneous resolution of clinical symptoms and wall motion abnormalities for the myocarditis group. RESULTS: MR imaging patterns were significantly different between the two cardiac disease groups (P < .05). All the patients with AMI had a segmental early subendocardial defect, with corresponding segmental subendocardial or transmural delayed high enhancement in a predominantly anteroseptal or inferior vascular distribution in 28 patients. All patients with AMI had stenosis of at least the infarct-affected coronary artery. All but one of the patients with myocarditis had no early defect and focal or diffuse nonsegmental nonsubendocardial delayed enhancement predominantly in an inferolateral location. CONCLUSION: Use of combined early- and late-perfusion MR imaging sequences helps to distinguish AMI from myocarditis.

Coronary Angiography↗