Reproducibility of manual and semi-automated late enhancement quantification in patients with Fabry disease.

BACKGROUND: Late enhancement (LE) imaging is increasingly used for diagnosis of non-ischemic cardiomyopathy. However, the mostly patchy appearance of LE in this context may reduce the reproducibility of LE measurement. PURPOSE: To report intra- and inter-observer variabilities of LE measurements in Fabry disease using manual and semi-automated quantification. MATERIAL AND METHODS: Twenty MRI data-sets of male patients aged 44 ± 7 years were analyzed twice (interval 12 months) by one observer and additionally once by a second observer. Left ventricular (LV) parameters were determined using cine MRI. Gradient-echo LE images were analyzed by manual planimetry and by a semi-automatic prototype software. Variabilities were determined by Bland-Altman analyses and additionally intra-class correlation coefficient (ICC) values were calculated to survey intra- and inter-observer reproducibility. RESULTS: The amount of LE was 5.2 ± 5.1 mL or 2.8 ± 2.6 % of LV mass (observer 2). LE was detected predominantly intramurally in a patchy pattern. All patients had LE restricted to the basal infero-lateral parts of the LV. The extent of LE correlated to LV mass (207 ± 70 g, P < 0.05, r = 0.6). The intra- and inter-observer variabilities were -0.6 to 1.0 mL and -0.7 to 1.6 mL, respectively (95% confidence intervals). ICC values were 0.981-0.999. The semi-automatic software allowed quantification of LE areas in all patients. The comparison of LE amount determined by semi-automatic software versus manual planimetry yielded an intra-observer variability ranging from -1.9 to 2.3 mL. CONCLUSION: Semi-automatic planimetry of patchy LE in patients with Fabry disease is feasible. The determined intra- and inter-observer variabilities for manual and semi-automatic planimetry were in the range of 20-40% of LE amount with high ICC values.

Remodeling of the infarct territory in the time course of infarct healing in humans.

OBJECT: To analyze the remodeling processes of the infarct territory in the time course of infarct healing. MATERIALS AND METHODS: Serial late enhancement (LE) studies were performed in 30 patients following reperfused myocardial infarction (MI) in the first and second week post-MI and after 3 months. To characterize infarct remodeling over time, the following variables were derived and analyzed in a blinded fashion: Infarct size (IS, in mm(3)), maximum infarct thickness (IT(max), mm), mean infarct thickness (IT(mean), mm) and the variability of infarct thickness (VIT=IT(max)/IT(mean)). Further, a new parameter for the assessment of infarct remodeling, the infarct extent (IE, mm(2)) was computed. IE quantifies IS in two dimensions along the heart's circumferential and longitudinal directions. IS was divided by the IE to obtain IT(mean). RESULTS: Overall infarct thickness was highly variable. Infarct shrinkage due to infarct thinning and IE reduction was found in the first months of healing. IS, IT(mean) and IT(max) significantly decreased during follow-up. There was a less consistent change of the IE: IE decreased in 75% of all infarcts from the first week up to 3 months post-MI, whereas 25% of infarcts expanded. Infarct thinning was found in almost all patients (92%), hence occurring in patients with infarct expansion and in patients without infarct expansion. CONCLUSION: Infarct thinning and-to a lesser extent-IE reduction, contribute to infarct shrinkage in the time course of infarct healing. Infarct thinning may occur without infarct expansion.

Intraindividual comparison of myocardial delayed enhancement MR imaging using gadobenate dimeglumine at 1.5 T and 3 T.

For contrast-enhanced imaging techniques relying on strong T1 weighting, 3 T provides increased contrast compared with 1.5 T. The aim of our study was the intraindividual comparison of delayed enhancement MR imaging at 1.5 T and at 3 T. Twenty patients with myocardial infarction were examined at 1.5 T and 3 T. Fifteen minutes after injection of contrast agent (0.1 mmol gadobenate dimeglumine per kg body weight), inversion recovery gradient recalled echo (IR-GRE) sequences were acquired (1.5 T/3 T: TR 11.0/9.9 ms, TE 4.4/4.9 ms, flip 30 degrees /30 degrees , slice thickness 6/6 mm) to assess myocardial viability. Two observers rated image quality (Wilcoxon signed rank test). Quantification of hyperenhanced myocardium and standardized SNR/CNR measurements were performed (Student's t test). There was no significant difference with respect to image quality (1.5 T/3 T: 3.5/3.3, p = 0.34, reader 1; 2.4/2.7, p = 0.12, reader 2) and infarction size (760 +/- 566/828 +/- 677 mm(2) at 1.5 T, 808 +/- 639/826 +/- 726 mm(2) at 3 T, reader 1/reader 2, p > 0.05). Mean SNR in hyperenhanced/normal myocardium was 19.2/6.2 at 1.5 T and 29.5/8.8 at 3 T (p < 0.05). Mean CNR was 14.3 at 1.5 T and 26.0 at 3 T (p < 0.05). Delayed enhancement MR imaging at 3 T is a robust procedure yielding superior tissue contrast at 3 T compared with 1.5 T which is, however, not reflected by increased image quality.

Evaluation of the nephrotoxicity of iodixanol in patients with predisposing factors to contrast medium induced nephropathy referred for contrast enhanced computed tomography.

To determine the risk of developing contrast induced nephropathy (CIN) in intermediate-risk patients receiving iodixanol, an iso-osmolar, dimeric non-ionic contrast agent, for CT in a clinical setting. Hundred consecutive patients referred for a contrast enhanced CT with a serum creatinine concentration>1.1mg/dl and/or a glomerular filtration rate (GFR)<90ml/min were included. Exclusion criteria were a serum creatinine>2.0mg/dl and a GFR<30ml/min or concurrent nephrotoxic agents. Between 60 and 140ml (mean 97+/-42ml) iodixanol (320mgI/ml) were administered at a flow of 2.5-3ml/s. Hydration with 500ml NaCl i.v. was performed before and after contrast injection. Follow-up was completed in 99 patients (age, 64+/-13 years, 68 men). CIN was defined as increase in serum creatinine concentration +0.5mg/dl or >25% above baseline within 72h after contrast administration. Serum creatinine concentration and GFR were 1.40+/-0.22, 1.29+/-0.29, and 1.26+/-0.29mg/dl and 52.2+/-13.9, 51.3+/-21.1, and 51.5+/-15.1ml/min on days 0, 3, and 7, respectively. Three out of 99 (3%) patients who received 90-110ml iodixanol revealed a CIN on day 3 without persistence on day 7. No specific therapy was needed. One out of 99 patients reported an exanthema on days 3 and 7. With the use of iodixanol in intermediate-risk patients, 3% of the patients develop CIN on day 3 without need for a specific therapy or persistence on day 7.

A prospective study comparing different iodine concentrations for triphasic multidetector row CT of the upper abdomen.

OBJECTIVES: To investigate the effect of different iodine concentrations at either constant injection or iodine administration rates but constant total iodine load on contrast enhancement of liver, pancreas and spleen by multidetector row CT. MATERIALS AND METHODS: One hundred and twenty consecutive patients (70+/-6 years) underwent triphasic liver CT at a four-channel multidetector-row CT using the non-ionic contrast medium iopromide. Patients were divided into six equal groups-I: 150 ml, 240 mg/ml at 4 ml/s; II: 120 ml, 300 mg/ml at 4 ml/s; III: 97.3 ml, 370 mg/ml at 4 ml/s; IV: 150 ml, 240 mg/ml at 5 ml/s; V: 120 ml, 300 mg/ml, 60 ml at 6 ml/s, 60 ml at 3 ml/s; VI: 97.3 ml, 370 mg/ml at 3.3 ml/s. ROIs were measured in the liver, the pancreas, and the spleen in unenhanced, arterial, portal venous, and equilibrium phase. RESULTS: At a constant injection rate of 4 ml/s, pancreatic enhancement over baseline only in the arterial phase was significantly higher at 370 mg/ml (58+/-15 HU versus 59+/-18 HU versus 74+/-20 HU for groups I-III, respectively (p<0.02)). Comparison of different iodine concentrations at constant iodine administration rate (groups II, IV and VI) and of all six protocols revealed no significant differences at either phase. CONCLUSIONS: At a constant iodine load and constant injection rates, the high-iodinated contrast agent iopromide at 370 mg/ml improves pancreatic enhancement in the arterial phase. At constant iodine load and constant iodine administration rates, there is no significant effect of different iodine concentrations.

Different reconstruction intervals for exclusion of coronary artery calcifications by retrospectively gated MDCT.

OBJECTIVE: Exclusion of coronary artery calcifications has a high negative predictive value for the diagnosis of coronary artery disease. However, it is known that significant differences in calcium scoring can occur because of the ECG trigger interval. Thus, the aim of the study was to evaluate the influence of different reconstruction intervals on detection of any coronary calcium by using MDCT and retrospective cardiac gating. CONCLUSION: For a true exclusion of coronary artery calcifications, different reconstruction intervals have to be evaluated.

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease.

AIMS: The aim of this clinical cross-sectional study was to investigate the cardiac interrelation of morphological and functional abnormalities in patients with Fabry disease. METHODS AND RESULTS: Fifty-one patients (5-78 years) were compared with 25 controls (8-77 years). In all subjects, end-diastolic thickness of the left ventricle was measured by echocardiography and ultrasonic peak systolic strain rate (SR) was extracted to assess regional myocardial function. Magnetic resonance imaging was performed to assess late-enhancement for the detection of myocardial fibrosis in Fabry patients (n=39). In patients, women <20 years of age had no hypertrophy, no late-enhancement, and normal radial and longitudinal function (SR longitudinal=-1.7+/-0.5 s(-1); P=n.s. compared with controls). Ten women, >20 years of age, had no hypertrophy, no late-enhancement, normal radial and longitudinal function in the septal wall, but reduced longitudinal function in the lateral wall (SR=-1.4+/-0.5 s(-1)). All male patients without hypertrophy and no late-enhancement had normal radial function but reduced longitudinal function in both the septal and lateral walls (SR=-1.3+/-0.3 s(-1)). Patients with hypertrophy but without late-enhancement (n=13) had reduced radial and longitudinal function. Twelve patients displaying hypertrophy and late-enhancement had severely reduced radial and longitudinal function (SR=-1.1+/-0.5 s(-1)). Two of them with the worst impairment of regional function (SR=-0.8+/-0.6 s(-1)) died in the follow-up period. CONCLUSION: These results illustrate the variation of morphological changes and its functional consequences in Fabry cardiomyopathy.

Comparison of different iodine concentrations for multidetector row computed tomography angiography of segmental renal arteries.

The aims of this study were (1) to assess the diagnostic performance of multidetector row computed tomography angiography (CTA) on imaging of renal artery branches and (2) to investigate the effect of different iodine concentrations at constant total iodine load and either constant injection rates or constant iodine administration rates. A number of 120 consecutive patients (71+/-6 years of age) underwent CTA of renal arteries (collimation 4 x 1 mm) using the nonionic contrast medium iopromide, and were divided into six equal groups: 1: 150 ml, 240 mg/ml at 4 ml/s; 2: 120 ml, 300 mg/ml at 4 ml/s; 3: 97.3 ml, 370 mg/ml at 4 ml/s; 4: 150 ml, 240 mg/ml at 5 ml/s; 5: 120 ml, 300 mg/ml, 60 ml at 6 ml/s, 60 ml at 3 ml/s; 6: 97.3 ml, 370 mg/ml at 3.3 ml/s. The image quality of the main renal arteries (n=240) and their first-order to fourth-order branches was scored as 0 for no visualization, 1 for only visualization, and 2 for diagnostic. All main renal arteries were diagnostic. First-order branches had score 2 in 38/40, 40/40, 37/40, 38/40, 39/40, and 40/40 patients for groups 1-6, respectively (p=0.34). Second-order branches were imaged best in group 2 (p<0.002)). Third-order branches had score 2 in only 1/40, 5/40, 1/40, 2/40, 0/40, and 2/40 renal arteries. Fourth-order branches were not imaged diagnostically. At a constant total iodine load, the main renal arteries and their first-order branches achieved diagnostic image quality at all iodine concentrations in four-channel multidetector row CTA for the protocols tested. Second-order renal artery branches were imaged best at 120 ml contrast medium with an iodine concentration of 300 mg/ml at 4 ml/s.

Detection of myocardial infarctions by acquisition-weighted 31P-MR spectroscopy in humans.

PURPOSE: To determine whether the recently applied technique of acquisition-weighted 31P-MR spectroscopy (AW-MRS) allows for the detection of depressed energy metabolism in patients with inferior wall myocardial infarctions. MATERIALS AND METHODS: Eight patients with subacute myocardial infarction and wall motion abnormalities restricted to the inferior wall were examined with a 1.5-T MR scanner. Global and regional left ventricular (LV) function was assessed by cine MRI, and the size and extent of myocardial infarction was assessed by late enhancement (LE). MRS was performed with an AW three-dimensional chemical shift imaging sequence. Phosphocreatine/ATP ratios were determined with the postprocessing model AMARES for four voxels positioned in the anterior, lateral, inferior, and septal parts of the LV. RESULTS: The LV ejection fraction (EF) was reduced to 37.5%+/-9.0%. Seven of eight patients had transmural LE in the inferior wall, and one patient showed subendocardial enhancement in the inferior-lateral parts. Phosphocreatine/ATP ratios of the inferior wall were significantly reduced (P <0.05) compared to all other parts of the LV (1.03 +/- 0.39 (inferior), 1.67 +/- 0.81 (lateral), 1.73 +/- 0.29 (anterior), and 1.49 +/- 0.31 (septal)). The ratios in five of seven patients with transmural enhancement were <1.00 in the inferior wall. CONCLUSION: Acquisition weighting allows for the detection of inferior wall infarctions in patients. Transmural signal enhancement is associated with significant depression of phosphocreatine/ATP ratios.

Time course of 23Na signal intensity after myocardial infarction in humans.

Experimental studies demonstrated persistently increased 23Na content in nonviable myocardium post-myocardial infarction (MI). We hypothesized that nonviable myocardium in humans would show elevated 23Na content at all stages of infarct development, and therefore could be imaged with 23Na MRI. Ten patients were examined on days 4, 14, and 90 after infarction, and five of these patients participated in a 12-month follow-up. Double angulated short-axis cardiac 23Na images were obtained with the use of a 23Na surface coil and an ECG-triggered, 3D gradient-echo sequence. 1H T2-weighted imaging (N = 9) was performed on days 4, 14, and 90. Wall motion was assessed by cine MRI, and the infarct size was determined by late enhancement on day 90. The 23Na signal intensity (SI) of infarcted myocardium was expressed as the percentage increase over 23Na SI of noninfarcted myocardium. All of the patients showed an area of elevated SI on 23Na and 1H T2-weighted images that correlated with wall motion abnormalities and late enhancement. 23Na SI was highest on day 4. It then decreased until day 90, but remained elevated (39% +/- 18%, 31% +/- 17%, 28% +/- 13% on days 4, 14, and 90, respectively, P = 0.001). No further decrease was found 1 year after infarction (25% +/- 7%, P = 0.89 vs. day 90). 1H T2-weighted SI decreased between days 4 and 14, but on day 90 only six of nine patients had a residual elevated SI. Thus, 23Na SI is elevated in nonviable infarction at all time points following MI, and 23Na MRI may become a suitable technique for imaging nonviable myocardium in humans.

Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study.

BACKGROUND: Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosylceramide clearance in the hearts of patients with Fabry disease. Whether these results can be translated into an improvement of myocardial function has yet to be demonstrated. METHODS AND RESULTS: Sixteen patients with Fabry disease who were treated in an open-label study with 1.0 mg/kg body weight of recombinant alpha-Gal A (agalsidase beta, Fabrazyme) were followed up for 12 months. Myocardial function was quantified by ultrasonic strain rate imaging to assess radial and longitudinal myocardial deformation. End-diastolic thickness of the left ventricular posterior wall and myocardial mass (assessed by magnetic resonance imaging, n=10) was measured at baseline and after 12 months of ERT. Data were compared with 16 age-matched healthy controls. At baseline, both peak systolic strain rate and systolic strain were significantly reduced in the radial and longitudinal direction in patients compared with controls. Peak systolic strain rate increased significantly in the posterior wall (radial function) after one year of treatment (baseline, 2.8+/-0.2 s(-1); 12 months, 3.7+/-0.3 s(-1); P<0.05). In addition, end-systolic strain of the posterior wall increased significantly (baseline, 34+/-3%; 12 months, 45+/-4%; P<0.05). This enhancement in radial function was accompanied by an improvement in longitudinal function. End-diastolic thickness of the posterior wall decreased significantly after 12 months of treatment (baseline, 13.8+/-0.6 mm; 12 months, 11.8+/-0.6 mm; P<0.05). In parallel, myocardial mass decreased significantly from 201+/-18 to 180+/-21 g (P<0.05). CONCLUSIONS: These results suggest that ERT can decrease left ventricular hypertrophy and improve regional myocardial function.

Evaluation of sodium T1 relaxation times in human heart.

PURPOSE: To evaluate the sodium longitudinal relaxation (T(1)) characteristics for myocardium and blood in humans. MATERIALS AND METHODS: Eleven healthy volunteers were examined by using a (23)Na heart surface coil at a 1.5 T clinical scanner equipped with a broadband spectroscopy option. (23)Na MR measurements were performed by using a three-dimensional spoiled gradient echo sequence (in-plane resolution, 3.5 mm x 7 mm; slice thickness, 24 mm; TE, 3.1 msec; bandwidth, 65 Hz/pixel; TR, 21 to 150 msec). RESULTS: Longitudinal T(1) relaxation time components were 31.6+/-7.0 msec and 31.1+/-7.5 msec for myocardium and blood, respectively. CONCLUSION: (23)Na T(1) relaxation times of myocardium and blood can be determined in humans. The results are in agreement with values obtained from animal studies.

Cardiac systolic rotation and contraction before and after valve replacement for aortic stenosis: a myocardial tagging study using MR imaging.

OBJECTIVE: Aortic stenosis leads to the derangement of cardiac function and contraction mode because of chronic pressure overload that is relieved after surgical valve replacement. The purpose of this study was to determine the changes in left ventricular systolic rotation and contraction using MR tagging in patients with aortic stenosis before and after surgical valve replacement compared with age-matched healthy volunteers. MATERIALS AND METHODS: Twelve patients with aortic stenosis were examined with an electrocardiographically triggered two-dimensional tagging sequence at 1.5 T before and 12 months after surgical valve replacement for the evaluation of wall function of the apical, mid ventricular, and basal levels. Eight healthy volunteers in the same age group served as the control group. RESULTS: Before surgery, all patients showed a significant increase of apical rotation (22.2 degrees +/- 5.9 degrees vs 10.3 degrees +/- 2.5 degrees, p < 0.0001) and overall left ventricular torsion (25.1 degrees +/- 6.6 degrees vs 14.5 degrees +/- 3.7 degrees, p < 0.001); basal rotation was not significantly different (-2.9 degrees +/- 2.1 degrees vs -4.2 degrees +/- 1.9 degrees, p = not significant) compared with the volunteer group. Apical rotation and torsion were negatively correlated with left ventricular mass (r = -0.73, p < 0.01, and r = -0.61, p < 0.05, respectively) and end-diastolic volume (r = -0.73, p < 0.01 and r = -0.64, p < 0.03, respectively). One year after surgery, basal rotation was reduced in the patients with aortic stenosis compared with the patients in the control group (-1.9 degrees +/- 1.8 degrees, p < 0.01). In comparison with preoperative values, apical rotation (14.2 degrees +/- 3.6 degrees, p < 0.01) also decreased but was still elevated, and this resulted in a normalization of left ventricular torsion (16.1 degrees +/- 3.7 degrees, p < 0.01). CONCLUSION: Surgical valve replacement for aortic stenosis leads to normalization of the left ventricular torsion 1 year after surgery. Pressure overload before surgery is associated with an increase of systolic left ventricular wringing motion, possibly serving as a compensatory mechanism. This mechanism declines with increasing left ventricular hypertrophy and dilatation.

Sodium T2* relaxation times in human heart muscle.

PURPOSE: To determine sodium transverse relaxation (T2*) characteristics for myocardium, blood and cartilage in humans. METHODS: T2* measurements were performed using a 3D ECG-gated spoiled gradient echo sequence. A 1.5 Tesla clinical scanner and a 23Na heart surface coil were used to examine eight healthy volunteers. In biological tissue, the sodium 23 nucleus exhibits a two-component T2 relaxation due to the spin 3/2 and its quadrupolar nature. The long T2* components of normal myocardium, blood, and cartilage were quantified. For myocardium, the T2* was determined separately for the septum, anterior wall, lateral wall, and posterior wall. RESULTS: The long T2* relaxation time components of 13.3 +/- 4.3 msec (septum 13.9 +/- 3.2 msec, anterior wall 13.8 +/- 5.4 msec, lateral wall 11.4 +/- 4.1 msec, posterior wall 14.1 +/- 3.7 msec), 19.3 +/- 3.3 msec, and 10.2 +/- 1.6 msec, were significantly different for myocardium, blood, and cartilage, respectively (P < 0.00001, Friedman's ANOVA). CONCLUSION: Measurement of 23Na T2* relaxation times is feasible for different regions of the human heart muscle, which might be useful for the evaluation of cardiac pathologies.