Impact of exercise rehabilitation on cardiac neuronal function in heart failure: an iodine-123 metaiodobenzylguanidine scintigraphy study

Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36–66 years) with stable chronic heart failure of NYHA class II–III and an initial resting radionuclide left ventricular ejection fraction (LVEF) <50% were enrolled in the study. Patients underwent progressive, supervised endurance training (treadmill test, Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a cardiac rehabilitation referral centre in order to measure exercise parameters. Planar ¹²³I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801±428 vs 1229±245 kpm·min^–1, P = 0.001), exercise duration (504±190 vs 649±125 s, P = 0.02), and myocardial MIBG uptake (135%±19% vs 156%±25%, P = 0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%±9% vs 21%±10%, p = NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. Received 23 September and in revised form 24 November 1997     

Dual time point fluorine-18 fluorodeoxyglucose positron emission tomography: a potential method to differentiate malignancy from inflammation and normal tissue in the head and neck

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies imaging FDG PET imaging is used to detect and stage head and neck cancers. However, the variable physiologic uptake of FDG in different normal structures as well as at inflammatory sites may either obscure a tumor focus or be falsely interpreted to represent tumor activity. Twenty-one patients (9 men, 12 women, median age 59) were scanned serially at two time points, one at 70 min (range 47–112) and the second at 98 min (77–142) after the intravenous injection of 4.3 MBq/kg of FDG. The mean interval between emission scans was 28 min (13–49). Transmission scans were performed and regions of interest (ROIs) were overlayed on the fully corrected images. Standardiued uptake values (SUVs) were generated for the cerebellum, tongue, larynx, every lesion, and a matched contralateral site. Follow-up and pathologic studies revealed 18 squamous cell carcinomas and nine inflammatory or infectious lesions. Tumor SUVs were 4.0±1.6 (mean ± SD) for the first scan and 4.5±2.2 for the second scan. Contralateral SUVs were 1.2±0.5 and 1.1±0.5 for the two scans. Tumor SUVs increased by 12%±12% as compared with a 5%±17% decrease for contralateral sites (P<0.05). SUVs for inflammatory sites (2.0±0.7 and 2.0±0.9), cerebellum (4.2±1.3 and 4.3±1.4), tongue (1.8±0.4 and 1.9±0.5) and larynx (1.5±0.6 and 1.5±0.6) remained constant over time (+0.6%, +2.8%, +1.4%, and –2.4%; P<0.05 when compared with tumor SUV changes). The ratio tumor/contralateral SUV increased by 23%±29% over time while this ratio for inflamed sites increased by only 5%±15% (P=0.07). The time interval between scans correlated with increase in SUV for tumors (r=0.55, P<0.05) but not for any of the other ROIs. Separation was superior when studies were performed more than 30 min apart (P<0.05). These preliminary data suggest that dual time point imaging compatible with a clinical study protocol is helpful in differentiating malignant lesions from inflammation and normal tissues, especially when separated by a sufficient time interval. Received 22 March and in revised form 29 April 1999     

Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus

The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55±11 vs 63±12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120±12 vs 145±16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1.81±0.29 vs 2.27±0.20, respectively, P<0.01). During the follow-up period (18± 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%±16.87% vs 12.89%±11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant statistical differences between the control group and non-survivors in terms of age (54±11 vs 73±11 years, respectively, P<0.01), H/M ratio (2.27± 0.20 vs 1.64±0.36, respectively, P<0.01) and %WR (12.89%±11.94% vs 42.52%±22.39%, respectively, P<0.01). In conclusion, cardiac sympathetic denervation using MIBG scintigraphy observed in hypertensive NIDDM patients, and was more profound in non-survivors. MIBG scintigraphy proved useful for the evaluation of NIDDM patients with new onset hypertension, and it was found that NIDDM patients with abnormalities on MIBG scintigraphy needed to be observe carefully. Received 1 April and in revised form 27 May 1999     

Noninvasive determination of myocardial blood flow, oxygen consumption and efficiency in normal humans by carbon-11 acetate positron emission tomography imaging

The aims of this study were: (1) to measure noninvasively and near simultaneously myocardial blood flow, oxygen consumption, and contractile function and (2) to analyze myocardial energy expenditure and efficiency at rest and during dobutamine stress in normal humans. Dynamic and gated carbon-11 acetate positron emission tomography (PET) imaging was performed in 11 normal subjects. The initial uptake of ¹¹C-acetate was measured to estimate myocardial blood flow. Oxygen consumption was derived from the monoexponential slope of the ¹¹C-clearance curve recorded during myocardial washout. ECG-gated systolic and diastolic images were acquired during the peak myocardial ¹¹C activity to measure left ventricular radius, myocardial wall thickness, and long axis length. Myocardial oxygen consumption and parameters of cardiac geometry were used to determine myocardial energetics and cardiac efficiency by tension-area area analysis. Myocardial blood flow averaged 0.8±0.06 ml min^–1 g^–1 at rest and 1.48±0.15 ml min^–1 g^–1 during dobutamine stress. Oxygen delivery and consumption were 151±13 and 88±15 μl O₂ min^–1 g^–1 at rest and increased to 291±31 and 216±31 μl O₂ min^–1 g^–1, respectively, during pharmacological stress (P<0.001). Oxygen extraction increased from 59%±8% at rest to 76%±9% during stress (P<0.001). Mechanical efficiency was 29%±6% at rest and 32%±6% during dobutamine stress (P=NS) while external work efficiency was 16%±6% at rest and increased to 21%±4% (P<0.01) during dobutamine stress. Stepwise linear regression analysis identified rate-pressure product and external cardiac work as major correlates of oxygen consumption. In summary, rapid dynamic and gated PET ¹¹C acetate imaging provides the unique capability to study noninvasively determinants of myocardial energy delivery, expenditure, and efficiency. Received: 15 March and in revised form 28 May 1999     

Assessment of reperfused myocardium using a new ischaemia-avid imaging agent, technetium-99m HL91: comparison with myocardial glucose uptake

We evaluated the efficacy of a new ischae-mia-avid imaging agent, technetium-99m labelled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (^99mTc- HL91) as a marker of myocardial viability in ischaemic and reperfused myocardium. The left coronary artery of rats was ligated for 15 or 60 min and released. The myocardium was reperfused for 60 min [stunned myocardium, or acute myocardial infarction (MI)] or 7 days (subacute MI). Thereafter, ^99mTc-HL91 and carbon-14 2-deoxyglucose (DG) were co-injected 30 min before sacrifice. We evaluated the myocardial accumulation of ^99mTc-HL91 and DG by dual-tracer ex vivo autoradiography. The uptake of each tracer in the myocardial region was normalized by that in the septum (control), and expressed as percent uptake (%HL or %DG, respectively). Individual hearts were also histopathologically examined. The %HL in the stunned myocardium (n = 8) and in the septum were identical (101%±15%, mean±SD, P = ns), whereas the %DG was significantly increased (149%±27%, P<0.05) compared with that in the septum. These results suggest that ^99mTc-HL91 cannot visualize stunned myocardium, whereas DG can. In acute MI (n = 7), the %HL (423%±96%, P<0.005) and the %DG (318%±91%, P<0.001) in the non-infarcted area at risk were significantly augmented compared with those in the septum. The %DG (181%±17%) in the infarcted area was also augmented (P<0.001), whereas the %HL (106%±25%) in the infarcted area was identical to that in the septum (P = ns). These results indicate that ^99mTc-HL91 detected viable myocardium in the area at risk. In subacute MI (n = 8), the%HL in the infarcted area (101%±45%) and in the septum was identical, whereas %DG (292%±57%) was significantly higher than that in the non-infarcted risk area or the septum (P<0.0001). These findings suggest that DG detected viable myocardium in the area at risk, but that ^99mTc-HL91 was not retained. We conclude that ^99mTc-HL91 is a potent marker of myocardial viability when used during the early acute phase after reperfusion. Received 9 September and in revised form 17 December 1997     

Role of positron emission tomography using fluorine-18 fluoro-2-deoxyglucose in predicting improvement in left ventricular function in patients with idiopathic dilated cardiomyopathy

Improvement in left ventricular (LV) function in patients with idiopathic dilated cardiomyopathy (DCM) by medical treatment has been suggested. Thus, it is important to evaluate which patients will respond to medical therapy. Positron emission tomography (PET) with fluorine-18 fluoro-2-deoxyglucose (FDG) and cardiac catheterization were performed in 20 patients with DCM before the initiation of medical therapy. The regional myocardial glucose utilization rate (rMGU) was measured with FDG PET. Subjects were divided into two groups, group 1 (event-free patients, n=10) and group 2 (clinical cardiac events, n=10). Haemodynamic and PET parameters before the initiation of medication were compared between the two groups and between patients with and patients without improvement in LV function. Ejection fraction (EF) was significantly higher in group 1 (35.8%±9.0%) than in group 2 (24.8%±7.0%) and LV end-diastolic pressure (LVEDP) was significantly lower in group 1 (8.4±1.7 mmHg) than in group 2 (11.6±3.5 mmHg). Average rMGU (mg min^–1 100 g^–1) was similar in group 1 (11.2±2.5 mg min^–1 100 g^–1) and group 2 (11.2±2.9 mg min^–1 100 g^–1), while %CV of rMGU was significantly lower in group 1 (11.1%±6.3%) than in group 2 (29.9%±13.9%, P<0.01). Furthermore, LV function normalized in seven patients in group 1. In these seven patients, EF (35.1%±10.9%), LVEDP (8.2±2.0 mmHg) and average rMGU (11.8±2.7 mg min^–1 100 g^–1) were comparable with those in patients without LV functional improvement (EF: 31.6%±9.1%; LVEDP: 10.7±3.3 mmHg; average rMGU: 10.8± 2.7 mg min^–1 100 g^–1). However,% CV of rMGU in patients with LV functional improvement (9.6%±5.6%) was significantly lower than in those without such improvement (26.3%±14.1%, P<0.01). %CV of rMGU <13.6% predicted prognosis with a sensitivity of 80%, a specificity of 100% and an accuracy of 90%. %CV of rMGU <13.6% also predicted improvement in LV function, with a sensitivity of 75%, a specificity of 92% and an accuracy of 85%. However, EF failed to predict improvement of LV function. In is concluded that homogeneous myocardial glucose utilization rate can predict both prognosis and improvement in LV function achieved by medical therapy in patients with DCM. Received 9 December 1997 and in revised form 11 March 1998     

Use of 123I-IMP brain SPET to predict outcome following STA-MCA bypass surgery: cerebral blood flow but not vasoreactivity is a predictive parameter

Superficial temporal artery – middle cerebral artery (STA-MCA) bypass surgery might improve the cerebral blood flow (CBF) but fail to reduce the risk of post-surgical events such as ischaemic stroke. In this study, we studied retrospectively whether the risk of post-surgical events corresponded to the change in resting CBF and/or the change in vasoreactivity observed before and after STA-MCA surgery using N-isopropyl-I-123-p-iodoamphetamine (¹²³I-IMP) brain single-photon emission tomography (SPET). ¹²³I-IMP brain SPET images obtained at rest and following acetazolamide challenge both before and after STA-MCA surgery were studied in 30 patients. Resting CBF was estimated semiquantitatively using the resting count ratios of the middle cerebral artery (MCA) area to the cerebellum. Acetazolamide challenge was assumed to result in an average increase in flow of 40% in the cerebellum. The vasoreactive response was then estimated as the ratio of the change in counts (acetazolamide – rest) to the resting cerebellar counts multiplied by 1.4. We classified 14 patients (50.5±19.3 years) into group I, who had a change in their resting CBF from before to after surgery of >10%, and 16 patients (54.0±18.8 years) into group II, who had a change in their resting CBF from before to after surgery of ≤10%. Oxygen-15 positron emission tomography (PET) studies were performed in five patients from group I and five patients from group II. One post-surgical event occurred in group I while there were eight post-surgical events in group II (P<0.05). Resting CBF improved by 20.4%±7.5% in group I and by 0.9%±6.9% in group II patients after surgery (P<0.001). No significant difference in the improvement in vasoreactivity was observed between group I patients (32.6%±17.7%) and group II patients (24.6%±15.6%) following surgery. Patients in the group I PET subset showed normalization of oxygen extraction fraction (OEF) from 0.59±0.09 before surgery to 0.46±0.06 after surgery (P<0.05), while patients in the group II PET subset showed no statistical difference in OEF before surgery (0.58±0.14) and after surgery (0.54± 0.05). We conclude that the outcome of STA-MCA bypass surgery can be predicted by the improvement in resting CBF but not by the improvement in vasoreactivity. Received 1 May and in revised form 3 August 1998     

Abnormal blood-pressure response to exercise and oxygen consumption in patients with hypertrophic cardiomyopathy

Background Abnormal blood-pressure response during exercise occurs in about one third of patients with hypertrophic cardiomyopathy (HCM), and it has been associated with a high risk of sudden cardiac death. We assessed the hemodynamics of exercise in HCM patients with abnormal blood-pressure response by using ambulatory radionuclide monitoring (VEST) of left-ventricular (LV) function, and exercise tolerance by oxygen consumption. Methods Twenty-two HCM patients uderwent treadmill exercise during VEST monitoring. A cardiopulmonary exercise test was performed a few days after. The VEST data were averaged for 1 minute. Stroke volume, cardiac output, and systemic vascular resistance were expressed as percent of baseline. Exercise tolerance was assessed as maximal oxygen consumption. Results In eight HCM patients (36%) with an abnormal blood-pressure response, endsystolic volume increased more (52%±21% vs 31%±28%, P=.012), and the ejection fraction (−31%±17% vs−14%±22%, P=.029) and stroke volume (−21%±21% vs 3%±28%, P=.026) fell more, than in patients with normal response. Cardiac output increased less in the former patients (49%±44% vs 94%±44%, P=.012). Systemic vascular resistance decreased similarly, irrespective of blood-pressure response (−28%±26% vs −34%±26%. P=N.S.). Percent of maximal predicted oxygen consumption was lower in HCM patients with an abnormal blood-pressure response (63%±11% vs 78%±15%, P=.025). Conclusions In HCM patients, abnormal blood-pressure response was associated with exercise-induced LV systolic dysfunction and impairment in oxygen consumption. This may cause hemodynamic instability, associated with a high risk of sudden cardiac death.     

Effect of temporal sampling on evaluation of left ventricular ejection fraction by means of thallium-201 gated SPET: comparison of 16- and 8-interval gating, with reference to equilibrium radionuclide angiography

Gated myocardial single-photon emission tomography (SPET) allows the evaluation of left ventricular ejection fraction (LVEF), but temporal undersampling may lead to systolic truncation and ejection fraction underestimation. The aim of this study was to evaluate the impact of temporal sampling on thallium gated SPET LVEF measurements. Fifty-five consecutive patients (46 men, mean age 62±12 years) with a history of myocardial infarction (anterior 31, inferior 24) were studied. All patients underwent equilibrium radionuclide angiography (ERNA) and gated SPET 4 h after a rest injection of 185 MBq (5 mCi) of thallium-201 using either 8-interval (group 1, n=25) or 16-interval gating (group 2, n=30). In group 2, gated SPET acquisitions were automatically resampled to an 8-interval data set. Projection data were reconstructed using filtered back-projection (Butterworth filter, order 5, cut-off 0.20). LVEF was then calculated using commercially available software (QGS). A higher correlation between gated SPET and ERNA was obtained with 16-interval gating (r=0.94) compared with the resampled data set (r=0.84) and 8-interval gating (r=0.71). Bland-Altman plots showed a dramatic improvement in the agreement between gated SPET and ERNA with 16-interval gating (mean difference: –0.10%±5%). Using multiple ANOVA, temporal sampling was the only parameter to influence the difference between the two methods. When using 8-interval gating, gated SPET LVEF was overestimated in women and underestimated in men (ERNA minus gated SPET = –4.0%±9.6% in women and 3.6%±7.6% in men, P=0.01). In conclusion, 16-interval thallium gated SPET offered the best correlation and agreement with ERNA, and should be preferred to 8-interval gated acquisition for LVEF measurement.     

Comparison of left ventricular contraction homogeneity index using SPECT gated blood pool imaging and planar phase analysis

Background  There is growing interest in developing a practical technique to accurately assess ventricular synchrony. We describe a novel 3-dimensional (3D) gated blood pool single photon emission computed tomography (SPECT) approach, from which a contraction homogeneity index (CHI) is derived and compared with planar phase analyses. Methods and Results  Subjects underwent planar and SPECT blood pool acquisition. Planar images were processed for left ventricular ejection fraction computation and phase values. SPECT images were processed by our novel algorithm, with which CHI was computed. Overall, 235 patients (79% male; mean age, 62±11 years) completed the study. Left ventricular ejection fractions were similar by planar (33.5%±13.5%) and 3D (34.7%±12.7%) methods (r=0.83, P<.0001). Mean phase angles for planar and tomographic methods were 126.3°±29.6° and 124.4°±28.7°, respectively (r=0.53, P<.0001). Phase and amplitude signals were incorporated in the CHI, which was non-normally distributed with a median of 73.8% (interquartile range, 58.7%–84.9%). This index minimized the negative impact of dyskinetic wall segments with limited regional motion. The planar heterogeneity index (SDΦ) was 28.2° (interquartile range, 17.5°–46.8°) and correlated inversely with CHI (r=−0.61, P<.0001). Conclusion  The novel 3D dispersion index CHI accounts for both phase delay of a dyssynchronous segment and its magnitude of contraction and is moderately correlated with planar phase analyses. Its potential in cardiac resynchronization therapy remains to be exploited. This work was supported in part by the “Fonds de la Recherche en Santé du Québec” and by a Canada Research Chair.     

Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate – comparison between the normal and failing human heart

The clearance kinetics of carbon-11 acetate, assessed by positron emission tomography (PET),can be combined with measurements of ventricular function for non-invasive estimation of myocardial oxygen consumption and efficiency. In the present study, this approach was applied to gain further insights into alterations in the failing heart by comparison with results obtained in normals. We studied ten patients with idiopathic dilated cardiomyopathy (DCM) and 11 healthy normals by dynamic PET with ¹¹C-acetate and either tomographic radionuclide ventriculography or cine magnetic resonance imaging. A ”stroke work index” (SWI) was calculated by: SWI = systolic blood pressure × stroke volume/body surface area. To estimate myocardial efficiency, a ”work-metabolic index” (WMI) was then obtained as follows: WMI = SWI × heart rate/k(mono), where k(mono) is the washout constant for ¹¹C-acetate derived from mono-exponential fitting. In DCM patients, left ventricular ejection fraction was 19%±10% and end-diastolic volume was 92±28 ml/m² (vs 64%±7% and 55±8 ml/m² in normals, P<0.001). Myocardial oxidative metabolism, reflected by k(mono), was significantly lower compared with that in normals (0.040±0.011/min vs 0.060± 0.015/min; P<0.003). The SWI (1674±761 vs 4736± 895 mmHg × ml/m²; P<0.001) and the WMI as an estimate of efficiency (2.98±1.30 vs 6.20±2.25×10⁶ mmHg × ml/m²; P<0.001) were lower in DCM patients, too. Overall, the WMI correlated positively with ejection parameters (r=0.73, P<0.001 for ejection fraction; r=0.93, P<0.001 for stroke volume), and inversely with systemic vascular resistance (r=–0.77; P<0.001). There was a weak positive correlation between WMI and end-diastolic volume in normals (r=0.45; P=0.17), while in DCM patients, a non-significant negative correlation coefficient (r=–0.21; P=0.57) was obtained. In conclusion non-invasive estimates of oxygen consumption and efficiency in the failing heart were reduced compared with those in normals. Estimates of efficiency increased with increasing contractile performance, and decreased with increasing ventricular afterload. In contrast to normals, the failing heart was not able to respond with an increase in efficiency to increasing ventricular volume. The present data support the usefulness of the WMI for non-invasive characterization of cardiac efficiency and may serve as a background for improved evaluation of medical therapy for heart failure. Received 10 August and in revised form 3 November 1999     

Normal uptake of <Superscript>18</Superscript>F-FDG in the testis: an assessment by PET/CT

Objective The aim of this study was to assess the physiological uptake of ¹⁸F-fluoro-2-deoxyglucose (FDG) by an apparently normal testis with combined positron emission tomography–computed tomography (PET/CT) and its correlation with age, blood glucose level, and testicular volume. Methods The testicular uptake of ¹⁸F-FDG, expressed as the standardized uptake value (SUV), was measured on PET/CT images in 203 men. The correlation between SUV and age, blood glucose level, and testicular volume was assessed. Results The SUV in the total of 406 testes was 2.44 ± 0.45 (range 1.23–3.85). The SUV was 2.81 ± 0.43 (2.28–3.85) for 30–39 years (n = 12), 2.63 ± 0.45 (1.77–3.75) for 40–49 years (n = 64), 2.46 ± 0.35 (1.44–3.15) for 50–59 years (n = 82), 2.51 ± 0.41 (1.50–3.46) for 60–69 years (n = 86), 2.43 ± 0.47 (1.42–3.29) for 70–79 years (n = 86), and 2.18 ± 0.45 (1.23–3.03) for 80–89 years (n = 76). When we calculated the mean SUV of bilateral testes in each patient, there were significant statistical differences between those in the age group of 30–39 years and 80–89 years, 40–49 years and 80–89 years, and 50–60 years and 80–89 years, when using an unpaired test with Bonferroni correction. The laterality index (|L − R|/(L + R) × 2) in 203 men was 0.066 ± 0.067 (0–0.522). There was a mild correlation between the mean SUV and age (r = −0.284, P < 0.001) as well as between the mean SUV and mean volume (r = +0.368, P < 0.001). There was no correlation between the mean SUV and glucose blood level (r = −0.065, P = 0.358). Conclusions Some uptake of FDG is observed in the normal testis and declines slightly with age. Physiological FDG uptake in the testis should not be confused with pathological accumulation.     

Reproducibility of polar map generation and assessment of defect severity and extent assessment in myocardial perfusion imaging using positron emission tomography

The purpose of this study was to determine the reliability of new software developed for the analysis of cardiac tomographic data. The algorithm delineates the long axis and defines the basal plane and subsequently generates polar maps to quantitatively and reproducibly assess the size and severity of perfusion defects. The developed technique requires an initial manual estimate of the left ventricular long axis and calculates the volumetric maximum myocardial activity distribution. This surface is used to map three-dimensional tracer accumulation onto a two-dimensional representation (polar map), which is the basis for further processing. The spatial information is used to compute geometrical and mechanical properties of a solid model of the left ventricle including the left heart chamber. A new estimate of the axis is determined from this model, and the previously outlined procedure is repeated together with an automated definition of the valve plane until differences between the polar maps can be neglected. This quantitative analysis software was validated in phantom studies with defects of known masses and in ten data sets from normals and patients with coronary artery disease of various severity. We investigated the reproducibility of the maps with the introduction of a similarity criterion where the ratio of two corresponding polar map elements lies within a 10% interval. The maps were also used to measure intra–and interobserver variability in respect of defect size and severity. In the phantom studies, it was possible to reliably assess mass information over a wide range of defects from 5 to 60 g (slope: 1.02, offset –0.68, r = 0.972). Patient studies revealed a statistically significant increase in the reproducibility of the automatic technique compared with the manual approach: 54%±19% (manual) compared with 88%±9% (automatic) for observer 1 and 61%±20% vs 82%±5% for observer 2, respectively. The intervariability analysis showed a significant improvement from 59%±14% to 83%±7% in similar polar map elements and a significantly improved correlation in the calculation of severity (from r = 0.908 to 0.989) and extent (from r = 0.963 to r = 0.992) of the perfusion defects when the automated procedure was applied. It is concluded that, assuming a constant wall thickness and tissue density, absolute defect mass can be reliably estimated. Furthermore, the proposed software demonstrates a significant improvement in the generation of volumetric polar maps for the quantitative assessment of perfusion defects. Received 15 April and in revised form 27 May 1998     

Biokinetics and radiation doses for carbon-14 urea in adults and children undergoing the Helicobacter pylori breath test

The long-term biokinetics and dosimetry of carbon-14 were studied in nine adults and eight children undergoing carbon-14 urea breath test for Helicobacter pylori (HP) infection. The elimination of ¹⁴C via exhaled air and urine was measured with the liquid scintillation counting technique and with accelerator mass spectrometry. After the subjects had been given 110 kBq ¹⁴C-urea (children: 55 kBq) orally, samples of exhaled air were taken up to 180 days after administration and samples of urine were collected up to 40 days. Sixteen of the subjects were found to be HP-negative. In these subjects a total of 91.1%±3.9% (mean of adults and children ± standard error of the mean) of the administered ¹⁴C activity was recovered. The majority of the administered activity, 88.3%±6.2% in adults and 87.7%±5.0% in children, was excreted via the urine within 72 h after administration. A smaller fraction was exhaled. In adults 4.6%±0.6% of the activity was exhaled within 20 days and in children 2.6%±0.3%. Uncertainties in the biokinetic results are mainly due to assumptions concerning endogenous CO₂ production and urinary excretion rate and are estimated to be less than 30%. The absorbed dose to various organs and the effective dose were calculated using the ICRP model for urea and CO₂. The urinary bladder received the highest absorbed dose: in adults, 0.15±0.01 mGy/MBq and in children of various ages (7–14 years), 0.14–0.36 mGy/MBq. The findings indicate that an investigation with ¹⁴C-urea gives an effective dose to adults of 2.1±0.1 μSv (for 110 kBq) and to children of 0.9–2.5 μSv (for 55 kBq). From a radiation protection point of view, there is thus no reason for restrictions on even repeated screening investigations with ¹⁴C-urea in whole families, including children. Received 27 October 1998 and in revised form 13 January 1999     

Use of Technegas as a radiopharmaceutical for the measurement of gastric emptying

Many radiopharmaceuticals and test meals that are used to measure gastric emptying are less than optimal. A vegetable-based solid meal, such as rice, labelled with a radiopharmaceutical that also has the capacity to measure gastric emptying of liquids, is likely to be ideal. The role of Technegas as a radioisotopic marker to measure gastric emptying of rice and liquids was evaluated. Technegas-labelled rice was incubated in 0.9% saline, 1 M HCl and simulated gastric fluid (3.2 g/l pepsinogen, pH 2–3) to assess stability of the label. In eight healthy volunteers gastric emptying of two meals – 200 g rice (370 kcal) and 75 g dextrose dissolved in 300 ml water (300 kcal), both labelled with 20 MBq of Technegas – was measured scintigraphically. Over 4 h, the average label stability was 93.7%±0.5% in 0.9% saline, 91.0%±0.4% in 1 M HCl and 93.6%±0.7% in simulated gastric juice. The lag phase was longer for rice than dextrose (25±7 min vs 4±2 min; P<0.05), but there was no difference in the post-lag emptying rate (2.1±0.3 kcal/min vs 1.7±0.2 kcal/min; P=0.2) between the two meals. We conclude that Technegas is a suitable radiopharmaceutical for measurement of gastric emptying of rice and nutrient-containing liquids. Received 8 March and in revised form 19 April 1999     

Age-related changes in cortical bone mass: data from a German female cohort

To describe data from digital radiogrammetry (DXR) in an unselected German female cohort over a wide age range. Using a retrospective study design we analyzed radiographs of the hand from 540 German women (aged 5–96 years) using an automated assessment of cortical thickness, metacarpal index (MCI), and estimated cortical bone mineral density (DXR-BMD) on digitized radiographs. Both hands were radiographed in 97 women. In this group DXR-BMD and cortical thickness were significantly higher in the right metacarpals while there was no significant difference in MCI. To study the association with age we differentiated young (<20 years), middle-aged (20–45 years), and an older patients (>45 years). In young women all parameters increased significantly with age in a linear fashion (r=0.8 for DXR-BMD, r=0.7 for MCI). In those aged 25–45 years DXR-BMD and MCI were highest (peak bone mass). In women aged 45 or older all parameters decreased with age in an almost linear fashion with an annual change ranging from 0.7% to 0.9%. Our results for an unselected German female cohort indicate that DXR is a reliable, widely available osteodensitometric technique based on the refinement of conventional radiogrammetry. These findings are comparable to those from other studies and represent a valid resource for clinical application and for comparisons with other ethnic groups.     

Doppler sonographic renal resistance index in healthy children

The objective of the study was to determine the values of Doppler resistance indices (RIs) in intrarenal arteries in healthy children. Color duplex Doppler sonography of intrarenal arteries was performed in 163 children and 58 adult patients, with the absence of clinical or laboratory pathologic changes of the urinary tract. All patients were classified following results of exploratory data analysis into three age groups: (a) 51 children between 2 and < 6 years of age; (b) 112 children 6–16 years of age; and (c) adults. The RIs were compared between different age groups. The mean RI ± 1 SD values in group 1 were 0.705 ± 0.018 (range 0.67–0.75), in group 2 0.605 ± 0.029 (range 0.55–0.65), and in the adult group 0.604 ± 0.035 (range 0.54–0.68). In the group of the youngest children (group 1), the RIs were significantly higher (p < 0.01) in comparison with the other group of children and the adult group. No statistically significant difference was observed between the group of children 6–16 years of age and the adult group. RI < 0.70 was noted in all children above 6 years of age; however, in younger children, RI ≥ 0.70 was observed in 72.5 % (37 of 51) of children. Resistance index in early childhood was considerably higher as compared with older children and the adult population: Apparently the RI value drops to adult level at approximately 6 years of age. The utilization of a threshold RI value of 0.70 for the increased renal vascular resistance in adults can also be applied to children over 6 years of age. Received: 4 January 2000; Revised: 3 April 2000; Accepted: 4 April 2000     

Coronary artery calcium score assessed by a 64 multislice computed tomography and early indexes of functional and structural vascular remodeling in cardiac syndrome X patients

Background. Regardless of normal coronary angiograms, coronary artery calcium (CAC) can be found in cardiac syndrome X (CSX) patients. According to some data, a relationship between the CAC score and markers of early atherosclerosis in CSX has been observed. Our aim was to assess whether the extent of the CAC score assessed by multislice computed tomography (MSCT) with a 64-slice system in CSX patients is related to brachial artery reactivity, intima-media thickness (IMT), and arterial compliance indexes. Methods and Results. High-resolution ultrasound was used to measure flow-mediated dilatation (FMD) and nitroglycerin-mediated vasodilatation, as well as the following parameters of arterial structural changes: IMT, pulse wave velocity, total arterial compliance, and stiffness index. MSCT was used to assess the presence and the quantity of CAC. The study group consisted of 46 CSX patients (mean age, 56.3±9 years), whereas the control group comprised 21 healthy subjects (mean age, 54.9±7 years). The assessment of the vascular parameters showed significantly decreased FMD and increased IMT in the CSX subjects (9.06%±3.2% and 0.67±0.1 mm, respectively) in comparison to the control subjects (17.42%±8.4% [P=.008] and 0.57 ± 0.2 mm [P=.021], respectively). CAC was detectable in 19 CSX patients (41%) (CAC range according to Agatston score, 2–500; mean, 101.6; median, 26.5) and in 1 control subject (4.8%) (CAC value, 13). CSX patients with detectable CAC were characterized by a significantly higher age (P=.001), lower body mass index (P=.017), and increased stiffness index (P=.020); there were no differences in FMD and IMT values. In a multivariate logistic and linear regression analysis, age was the only risk factor independently associated with the presence of CAC (P=.001) and the log(CAC+1) value (P=.01). In the subgroup of women, log(CAC+1) significantly correlated with age (r=0.587, P=.002) and stiffness index (r=0.427, P=.024), and in a borderline significant manner, it correlated with weight (r=−0.329, P=.07) and waist-hip ratio (r=0.315, P=.07). There were no significant correlations in the male subgroup. Conclusions. Low ranges of CAC are frequently detectable in CSX patients, and the results are age-related and independent of impaired early indexes of functional and structural vascular remodeling.     

Regional myocardial wall thickening and global ejection fraction in patients with low angiographic left ventricular ejection fraction assessed by visual and quantitative resting ECG-gated 99mTc-tetrofosmin single-photon emission tomography and magnetic resonance imaging

We investigated the use of visual and quantitative technetium 99m tetrofosmin ECG-gated single-photon emission tomography (SPET) for the assessment of regional myocardial wall thickening (WT) and left ventricular (LV) ejection fraction (EF) in comparison with gated magnetic resonance imaging (MRI) in patients with a low angiographic LVEF. Gated SPET using ^99mTc-labelled flow tracers offers potential for simultaneous assessment of myocardial perfusion and LV function. Few data are available on the use of visual and quantitative gated SPET in patients with low LVEF. In this study 21 patients with low angiographic LVEF (mean 37%±5%) were studied. Resting gated ^99mTc-tetrofosmin SPET and gated MRI were performed within 48 h. WT was assessed by visual interpretation (five point score) and quantitative analysis based on count increase. There was good agreement for EF measurements by MRI and gated SPET (mean EF: 33%±12% vs 35%±11%, r = 0.86, P<0.001). Areas under receiver operator characteristic curves (AUC) for differentiation between MRI WT score points ranged from 0.60 to 0.66 for visual SPET WT analysis, from 0.59 to 0.71 for delta count increase values and from 0.46 to 0.60 for % WT, indicating substantial overlap between WT categories. Absolute agreement for visual WT between MRI and gated SPET ranged from 25% to 57% (kappa 0.03–0.25) depending on tracer uptake, and was limited in areas with moderate to severe perfusion defects (kappa 0.03–0.13). It is concluded that gated SPET provided reliable estimates of regional WT and global function in patients with low angiographic LVEF. Received 15 October 1997 and in revised form 31 January 1998