Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [¹³N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min^–1·100 g^–1; group B, 124±30 ml·min^–1·100 g^–1 normal subjects, 105±21 ml·min^–1·100 g^–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.     

Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

Purpose Tetrahydrobiopterin (BH₄) is an essential co-factor for the synthesis of nitric oxide (NO), and BH₄ deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH₄ deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia.Methods Myocardial blood flow (MBF; ml min^–1 g^–1) was measured at rest, during adenosine-induced (140 g kg^–1 min^–1 over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using ¹⁵O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH₄ (10 mg kg^–1 body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress.Results BH₄ increased exercise-induced hyperaemia in controls (2.96±0.58 vs 3.41±0.73 ml min^–1 g^–1, p<0.05) and hypercholesterolaemic subjects (2.47±0.78 vs 2.70±0.72 ml min^–1 g^–1, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52±1.10 vs 4.85±0.45 ml min^–1 g^–1, p=NS) or hypercholesterolaemic subjects (4.86±1.18 vs 4.53±0.93 ml min^–1 g^–1, p=NS). Flow reserve utilisation remained unchanged in controls (70±17% vs 71±19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53±15% vs 66±14%, p<0.05).Conclusion BH₄ restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH₄ deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.The first two authors have contributed equally to the present project.An erratum to this article can be found at     

Dual-energy perfusion-CT of pancreatic adenocarcinoma

Purpose

To evaluate the feasibility of dual-energy CT (DECT)-perfusion of pancreatic carcinomas for assessing the differences in perfusion, permeability and blood volume of healthy pancreatic tissue and histopathologically confirmed solid pancreatic carcinoma.

Materials and methods

24 patients with histologically proven pancreatic carcinoma were examined prospectively with a 64-slice dual source CT using a dynamic sequence of 34 dual-energy (DE) acquisitions every 1.5 s (80 ml of iodinated contrast material, 370 mg/ml, flow rate 5 ml/s). 80 kV_p, 140 kV_p, and weighted average (linearly blended M0.3) 120 kV_p-equivalent dual-energy perfusion image data sets were evaluated with a body-perfusion CT tool (Body-PCT, Siemens Medical Solutions, Erlangen, Germany) for estimating perfusion, permeability, and blood volume values. Color-coded parameter maps were generated.

Results

In all 24 patients dual-energy CT-perfusion was. All carcinomas could be identified in the color-coded perfusion maps. Calculated perfusion, permeability and blood volume values were significantly lower in pancreatic carcinomas compared to healthy pancreatic tissue. Weighted average 120 kV_p-equivalent perfusion-, permeability- and blood volume-values determined from DE image data were 0.27 ± 0.04 min⁻¹ vs. 0.91 ± 0.04 min⁻¹ (p < 0.0001), 0.5 ± 0.07 *0.5 min⁻¹ vs. 0.67 ± 0.05 *0.5 min⁻¹ (p = 0.06) and 0.49 ± 0.07 min⁻¹ vs. 1.28 ± 0.11 min⁻¹ (p < 0.0001). Compared with 80 and 140 kV_p the standard deviations of the kV_p120 kV_p-equivalent values were manifestly smaller.

Conclusion

Dual-energy CT-perfusion of the pancreas is feasible. The use of DECT improves the accuracy of CT-perfusion of the pancreas by fully exploiting the advantages of enhanced iodine contrast at 80 kV_p in combination with the noise reduction at 140 kV_p. Therefore using dual-energy perfusion data could improve the delineation of pancreatic carcinomas.     

Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

Purpose Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means.Methods One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF 40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with ¹⁵O-labelled water (H₂¹⁵O) and ¹⁸F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (0.6 ml min^–1 g^–1) were classified as stunned, and segments with reduced MBF (<0.6 ml min^–1 g^–1) as hibernating if MRG was 0.25 mol min^–1 g^–1. Segments with reduced MBF and MRG <0.20 mol min^–1 g^–1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 mol min^–1 g^–1 as non-transmural scars.Results Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 mol min^–1 g^–1) and 233 (39%) reduced MRG (0.16±0.05 mol min^–1 g^–1). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 mol min^–1 g^–1) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min^–1 g^–1), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min^–1 g^–1 and 0.48±0.08 ml min^–1 g^–1, respectively), and lowest in transmural scars (0.40±0.14 ml min^–1 g^–1, P<0.01). MRG was comparable in hibernating and stunned myocardium with preserved MRG (0.40±0.19 mol min^–1 g^–1 vs 0.46±0.20 mol min^–1 g^–1, NS), and lowest in stunned myocardium with reduced MRG and transmural scars.Conclusion Chronic stunning is more prevalent than expected. The degree of MRG reduction in stunned myocardium may disclose segments at higher risk of permanent damage.     

Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123±7/65±9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8±0.6 vs 2.5±1.0 ml min^–1 g^–1; P<0.05), and perfusion reserve was also lower, at borderline significance (2.7±1.0 vs 3.6±1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9±0.9 (P<0.001) due to normalisation of maximal perfusion (2.3±0.5 ml min^–1 g^–1, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH.     

Clearance of thallium-201 from the peripheral blood: Comparison of immediate and standard thallium-201 reinjection

As several reinjection procedures have shown encouraging results in terms of imaging, we investigated whether the kinetics of thallium-201 would differ between the standard stress-redistribution-reinjection approach and the stress-immediate reinjection approach. In 53 consecutive patients with undiagnosed chest pain, 75 MBq (2 mCi)²⁰¹Tl was injected at maximal exercise. In 26 of these patients (group I), 37 MBq (1 mCi)²⁰¹Tl was reinjected immediately after completing the exercise images (the immediate reinjection procedure) and in 27 patients (group II), 37 MBq (1 mCi)²⁰¹Tl was reinjected after completing 3-h redistribution images (the standard reinjection procedure). Mean peak²⁰¹Tl blood activity after exercise was 17.7±12.5 kBq/ml (4.8±3.4 mCi/ml) for group I versus 16.4±9.2 kBq/ml (4.4±2.5 mCi/ml) for group II (NS). The relative increase in²⁰¹Tl blood activity after reinjection of half the initial dose [37 MBq (1 mCi)] exceeded 50% of the initial peak in both groups. The relative amount of²⁰¹Tl delivered to the myocardium was assessed by the area under the curve after both exercise and reinjection, and was 117%±72% for group I and 112%±73% for group II (NS). Blood clearance of²⁰¹Tl was at least biexponential. Mean early decay constants (₁) after exercise and reinjection were 0.30±0.18 min^–1 and 0.22±0.046 min^–1 respectively for group I (T _1/2 2.3 min and 3.2 min respectively, NS), and 0.30±0.12 min^–1 and 0.24±0.07 min^–1 respectively for group II (T _1/2 2.3 min and 2.9 min respectively, NS). For both procedures no significant differences were found between ₁ after exercise and ₁ after injection. The mean late clearance (₂) from the blood was 0.032±0.056 min^–1 and 0.012±0.012 min^–1 respectively for group I (T _1/2 21.6 min and 57.7 min respectively, NS), and 0.036±0.030 min^–1 and 0.014±0.014 min^–1 respectively for group II (T _1/2 19.3 min and 49.5 min respectively, NS). Also, no significant differences were found between ₂ after exercise for both groups and between ₂ after reinjection for both groups. We conclude that reinjection of 37 MBq (1 mCi)²⁰¹Tl (half the initial dose) results in a relative increase in the initial peak and a relative increase in the amount of²⁰¹Tl delivered to the myocardium of more than 50% for both the standard and the immediate reinjection procedure. The clearance of²⁰¹Tl from the blood was not influenced by exercise or by the time of reinjection. Based on²⁰¹Tl kinetics as measured in the peripheral blood, there is no reason to postpone reinjection until 3–4 h following exercise.     

Effect of scatter correction on the compartmental measurement of striatal and extrastriatal dopamine D<Subscript>2</Subscript> receptors using [<Superscript>123</Superscript>I]epidepride SPET

Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D₂ receptors using [¹²³I]epidepride. Eight healthy human subjects [age 30±8 (range 22–46) years] participated in a study with a bolus injection of 373±12 (354–389) MBq [¹²³I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry (SC) and without scatter correction using broad-beam (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1–1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [¹⁸F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies.     

Kinetics of [<Superscript>11</Superscript>C]choline uptake in prostate cancer: a PET stydy

Carbon-11 choline has recently been introduced as a potential tracer for tumour imaging with positron emission tomography (PET). We evaluated the kinetics of the uptake of [¹¹C]choline in prostate cancer and benign prostatic hyperplasia. We also evaluated the association between the uptake of [¹¹C]choline and the histological grade of malignancy, Gleason score, volume of the prostate and prostate-specific antigen (PSA). Fourteen patients with histologically confirmed prostate cancer and five patients with benign prostatic hyperplasia were studied with [¹¹C]choline PET. A mean dose of 430±31 MBq of [¹¹C]choline was injected intravenously and a dynamic emission acquisition of prostate was performed for 30 min. The uptake of [¹¹C]choline was measured as a standardised uptake value (SUV) and as a kinetic influx constant (K _i) obtained from graphical analysis. Both cancerous and hyperplastic prostate were well visualised with [¹¹C]choline against low or moderate tracer accumulation in the bladder and rectal wall. The measured radioactivity in urine was invariably low. In the graphical analysis, linear plots were achieved. The mean K _i of the untreated tumour was 0.205±0.089 min^–1 (range 0.128–0.351; n=7) and the mean SUV was 5.6±3.2 (range 1.9–15.5; n=15). K _i values and SUVs correlated closely (r=0.964, P=0.0005), whereas no correlation could be demonstrated between the tumour uptake of [¹¹C]choline and the histological grade, Gleason score, volume of the prostate or PSA . The mean SUV and the mean K _i of benign hyperplastic prostate were 3.5±1.0 (range 2.0–4.5; n=4) and 0.119±0.076 min^–1 (range 0.065–0.173; n=2). In conclusion, a high uptake of [¹¹C]choline characterises not only carcinomatous but also hyperplastic prostatic tissue. Dynamic imaging of the uptake of [¹¹C]choline in the prostate shows a good applicability of the graphical analysis model with an irreversible compartment. A close correlation between the K _i values and semiquantitative SUVs of tumours supports the use of the simpler SUV in the clinical setting.     

Regional perfusion,oxygen metabolism,blood volume and immunoglobulin G accumulation at focal sites of infection in rabbits

Infection causes remarkable changes in extracellular fluid volume, blood flow and oxygen consumption in the region of the lesion. To determine the sequence and magnitude of these changes, we performed serial scintigraphic measurements in 10 rabbits with experimental Escherichia coli abscesses. Positron emission tomography with C¹⁵O₂, ¹⁵O₂ and ¹¹CO was used to measure regional blood flow, oxygen extraction (OEF) and blood volume; extracellular fluid volume was evaluated by single photon scintigraphy with indium-111 immunoglobulin G (IgG). Images were recorded following tracer administration at 1 and 7–10 days after infection. At the first imaging time, blood flow to infected muscle had increased by 40% compared with control sites (7.4±0.6 to 10.8 ± 3.8 ml/min · 100 g), OEF had decreased from 55%±34% to 45%±14%, and the infected-tocontralateral (I/C) ratio of IgG had increased to 3.34±1.85. At the later imaging time, flow had increased by almost threefold compared with day 1 (29.4±9.8 ml/min · 100 g), OEF had decreased to 29%±14%, and the I/C ratio for IgG had remained constant. Although OEF fell,oxygendelivery (OEF × flow) increased from 4.07 ml/min (control value) to 4.86 ml/min on day 1 and 8.64 ml/min on days 7–9. The infected-to-contralateral (IC) ratio of ¹⁵02/C¹⁵O₂ was 0.74±0.15 on day 1 and 0.77±0.10 at 7–9 days. These studies indicate that expansion of the extracellular fluid volume increases early in the evolution of the infection and exceeds changes in regional perfusion and oxygen delivery.     

The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels

Purpose The aim of this study was to investigate the role of thymidine kinase 1 (TK₁) protein in 3-deoxy-3-[¹⁸F]fluorothymidine ([¹⁸F]FLT) positron emission tomography (PET) studies.Methods We investigated the in vivo kinetics of [¹⁸F]FLT in TK₁+/– and TK₁–/– L5178Y mouse lymphoma tumours that express different levels of TK₁ protein.Results [¹⁸F]FLT-derived radioactivity, measured by a dedicated small animal PET scanner, increased within the tumours over 60 min. The area under the normalised tumour time–activity curve were significantly higher for the TK₁+/– compared with the –/– variant (0.89±0.02 vs 0.79±0.03 MBq ml^–1 min, P=0.043; n=5 for each tumour type). Ex vivo gamma counting of tissues excised at 60 min p.i. (n=8) also revealed significantly higher tumour [¹⁸F]FLT uptake for the TK₁+/– variant (6.2±0.6 vs 4.6±0.4%ID g^–1, P=0.018). The observed differences between the cell lines with respect to [¹⁸F]FLT uptake were in keeping with a 48% higher TK₁ protein in the TK₁+/– tumours versus the –/– variant (P=0.043). On average, there were no differences in ATP levels between the two tumour variants (P=1.00). A positive correlation between [¹⁸F]FLT accumulation and TK₁ protein levels (r=0.68, P=0.046) was seen. Normalisation of the data for ATP content further improved the correlation (r=0.86, P=0.003).Conclusion This study shows that in vivo [¹⁸F]FLT kinetics depend on TK₁ protein expression. ATP may be important in realising this effect. Thus, [¹⁸F]FLT-PET has the potential to yield specific information on tumour proliferation in diagnostic imaging and therapy monitoring.     

Quantitative determination of regional extravascular lung water and regional blood volume in congestive heart failure

Regional extravascular lung water (rELW) and blood volume (rBV) in five controls and 14 patients with congestive heart failure (CHF) were measured by constant infusion of H₂ ¹⁵O and inhalation of ¹¹CO using positron emission tomography (PET). The analysis of 18 regions per patient revealed a relatively homogenous level of rELW in the controls (x=0.11±0.02 g/cc; range, 0.08–0.21), whereas this increased in patients with CHF (0.17±0.02 g/cc; range, 0.10–0.51). The rBV was 0.21±0.02 g/cc in the controls and 0.17±0.02 g/cc in patients with CHF. A good correlation was found between the severity of chronic heart failure (according to the grading of the New York Heart Association) and mean extravascular lung water (ELW) (r=0.69), as well as between CHF and the ratio rELW/rBV (r=0.87); however, the correlation to hemodynamic data was less satisfactory (cardiac index, r=0.45; pulmonary capillary wedge pressure, r=0.47; ejection fraction, r=0.60). In supine controls, a progressive decrease in regional blood volume from the basal to the apical regions was observed, whereas the differences in ELW were only small. In patients with chronic heart failure, ELW in the basal parts was markedly increased, whereas in the apical regions, only minor deviations from the controls were observed. In the basal regions of these patients, the blood volume was reduced by about 30%. Instead of the normal basoapical gradient of blood volume, these patients showed a rather flat distribution. Radiographic findings of pulmonary edema generally appeared together with an ELW level of greater than 0.14 g/cc. We conclude that the amount and distribution of fluid in pulmonary congestion can be noninvasively assessed by PET.Dedicated to Prof. Dr. Hans-Stephan Stender on his 65th birthday     

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (K_mono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112±0.020 min^–1 vs 0.065±0.015 min^–1 at rest) (P<0.001) in proportion to the increase in the pressure-rate product. K_mono in the right ventricular (RV) myocardium also increased (0.080±0.018 min^–1 vs 0.034±0.013 min^–1 at rest) (P<0.001), with an excellent correlation with the LV K_mono (r=0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158%±81%) than that in LV Kmono (79%±39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects. Correspondence to: N. Tamaki     

Demonstration of disturbed free fatty acid metabolism of myocardium in patients with non-insulin-dependent diabetes mellitus as measured with iodine-123-heptadecanoic acid

Myocardial free fatty acid metabolism and left ventricular function were evaluated in 15 middle-aged patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 8 healthy control subjects. The study subjects had no evidence of coronary heart disease on the basis of clinical history, exercise ECG or myocardial perfusion scintigraphy. During peak exercise, iodine-123 hepatadecanoic acid (HDA) was intravenously injected. Myocardial activity distribution of ¹²³I-HDA was measured 10, 30, and 50 min after exercise using single-photon emission tomography (SPET); and then further corrected by free ¹²³I-iodine. Venous blood samples were drawn for detecting the plasma activity of ¹²³I. The net extraction of ¹²³I-HDA into the myocardium was obtained by dividing the corrected tissue ¹²³I concentration by the integral of the plasma time activity curve. The net extraction was 0.40 ± 0.06 min^–1 (mean ± SD) patients with NIDDM and 0.38 ± 0.06 min^–1 in control subjects (P>0.1), respectively. The faster elimination rate of ¹²³I-HDA was found in patients with NIDDM (0.029±0.008 min^–1) than in control subjects (0.022±0.004 min^–1; P<0.01). There was no statistically significant difference in left ventricular ejection fraction (LVEF) at rest between patients with NIDDM (53±9%) and control subjects (56±2%), whereas the increase of LVEF during exercise remained lower in patients with NIDDM (3.4±8.2%) than in control subjects (11.8±5.8%; P<0.025). A significant correlation (r=0.64; P < 0.01) was found between the net extraction of ¹²³I-HDA and the change of LVEF, as well as with exercise load (r=0.68; P<0.01). In conclusion, evidence of an increased fatty acid utilization and triglyceride synthesis rate was observed in the diabetic myocardium. Offprint requests to: J.T. Kuikka     

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C¹⁵O₂) or ¹⁵O-labelled water (H₂ ¹⁵O), ¹⁵O-labelled carbon monoxide (C¹⁵O) and ¹⁵O-labelled oxygen (¹⁵O₂) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of ¹⁵O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C¹⁵O₂ (or H₂ ¹⁵O) and ¹⁵O₂. All used C¹⁵O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml^–1 min^–1; CBV=3.8±0.7 ml 100 ml^–1; OEF=0.44±0.06; CMRO₂=3.3±0.5 ml 100 ml^–1 min^–1. Significant between-centre variation was observed in CBV, OEF and CMRO₂ by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO₂ was acceptably small. Building a database of normal cerebral haemodynamics obtained by the¹⁵O-PET methods may be practicable.     

Quantitative analysis of myocardial glucose utilization in patients with left ventricular dysfunction by means of 18F-FDG dynamic positron tomography and three-compartment analysis

Purpose Myocardial glucose utilization (MGU) is altered in various heart diseases. The aim of this study was to quantitatively assess regional myocardial glucose utilization in patients with left ventricular (LV) dysfunction by dynamic ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET).Methods A total of 18 subjects were studied, including ten with LV dysfunction (seven with idiopathic dilated cardiomyopathy and three with aortic regurgitation; NYHA II in 8 and III in 2) and eight healthy normal volunteers. Patients with diabetes mellitus were excluded. A dynamic PET study was performed for 40 min following the injection of 370 MBq of FDG after 50-g glucose loading. On the basis of a three-compartment model, MGU, K₁, k₂, and k₃ were computed on a pixel by pixel basis to generate LV myocardial parametric maps. FDG standardized uptake value (SUV) was also calculated using static images obtained 40 min after FDG injection. These metabolic values were compared with myocardial flow distribution (%Flow), LVEF, LV volumes, and LV wall thickening (WT) determined by gated myocardial single-photon emission computed tomography using QGS software in eight myocardial segments.Results MGU correlated positively with LV volumes and negatively with LVEF. K₁ was significantly higher in the segments of the patients than in those of the normal volunteers (0.082±0.055 vs 0.041±0.017 ml min^–1 g^–1, p<0.05), although there was no difference in MGU between the groups. On the other hand, SUV, k₂, and k₃ did not differ significantly between the groups. Among the patients, the K₁ values were significantly higher in the areas with impaired WT (%WT<17%) (0.109±0.063 vs 0.069±0.062 ml min^–1 g^–1, p<0.05) and in the areas with flow reduction (%Flow<71%) (0.112±0.076 vs 0.071±0.046 ml min^–1 g^–1, p<0.05).Conclusion These results indicate that glucose utilization was preserved in the patients with LV dysfunction, mainly due to an increase in glucose transport, particularly in the regions with severely impaired LV function. Thus, the quantitative assessment of myocardial glucose utilization by FDG dynamic PET may provide useful information for assessing the regional myocardial metabolic status in patients with LV dysfunction.     

High‐resolution longitudinal assessment of flow and permeability in mouse glioma vasculature: Sequential small molecule and SPIO dynamic contrast agent MRI

The poor prognosis associated with malignant glioma is largely attributable to its invasiveness and robust angiogenesis. Angiogenesis involves host–tumor interaction and requires in vivo evaluation. Despite their versatility, few studies have used mouse glioma models with perfusion MRI approaches, and generally lack longitudinal study design. Using a micro‐MRI system (8.5 Tesla), a novel dual bolus‐tracking perfusion MRI strategy was implemented. Using the small molecule contrast agent Magnevist, dynamic contrast enhanced MRI was implemented in the intracranial 4C8 mouse glioma model to determine K^trans and v_e, indices of tumor vascular permeability and cellularity, respectively. Dynamic susceptibility contrast MRI was subsequently implemented to assess both cerebral blood flow and volume, using the macromolecular superparamagnetic iron oxide, Feridex, which circumvented tumor bolus susceptibility curve distortions from first‐pass extravasation. The high‐resolution parametric maps obtained over 4 weeks, indicated a progression of tumor vascularization, permeability, and decreased cellularity with tumor growth. In conclusion, a comprehensive array of key parameters were reliably quantified in a longitudinal mouse glioma study. The syngeneic 4C8 intracerebral mouse tumor model has excellent characteristics for studies of glioma angiogenesis. This approach provides a useful platform for noninvasive and highly diagnostic longitudinal investigations of anti‐angiogenesis strategies in a relevant orthotopic animal model. Magn Reson Med 61:615–625, 2009. © 2009 Wiley‐Liss, Inc.     

MRI measurements of the pons and cerebellum in children born preterm; associations with the severity of periventricular leukomalacia and perinatal risk factors

Our purpose was to measure the size of the pons and cerebellum in preterm babies with periventricular leukomalacia (PVL), and to study their relationship with the severity of PVL and with perinatal risk factors. We examined 33 premature children, mean gestational age 31 weeks, range 26–36 weeks with PVL on MRI, and 27 full-term controls. On MRI at 0.4–5.5 years (mean 1.4 years) we measured the area of the corpus callosum and vermis, the anteroposterior diameter of the pons and the volume of the cerebellum. The area of the corpus callosum was used as a marker of white matter loss and PVL severity. All regional brain measurements except that of the vermis were significantly lower in patients than controls: corpus callosum (mm²): 239.6±92.5 vs 434.8±126.8, P <0.01; pons (mm): 14.8±3.0 vs 17.9±1.4, P <0.01]; cerebellum (cm³): 68.2±31.6 vs 100.6±28.3, P <0.01; vermis (mm²): 808.1±292.2 vs 942.2±246.2, NS. Significant reduction in the area of the vermis: 411.3±203.3 vs 935±252.6 mm²; cerebellar volume: 16.3±12.5 vs 96.6±20.2 mm³; and the diameter of the pons: 10.1±2.2 vs 17.5±1.3 mm (P <0.01) were observed in seven children with gestational age 28 weeks, severe hypotension and large patent ductus arteriosus (PDA). There was a significant correlation between the duration of mechanical ventilation and the size of the vermis, pons and cerebellum (R=–0.65, –0.57 and –0.73, respectively, P <0.01).     

Quantification of baboon cortical S2 serotonin receptors in vivo with 3-N-(2′-Fl8)fluoroethylspiperone and positron emission tomography

We used the ligand 3-N-(2-F 18)fluoroethylspiperone (FESP) and positron emission tomography (PET) to quantify in vivo serotonin S₂ neuroreceptor density and affinity in the baboon frontal cortex. In the cortex, FESP binds specifically and exclusively to S₂ receptors, and an equilibrium is reached when the rate of ligand-receptor association and dissociation become equal. Using multiple studies in the same baboon, an equilibrium (saturation) analysis approach provided a linear Hill plot with a slope of 1.02 (r ² =0.988,P <0.0001), indicative of ligand binding to a single receptor class. Using serial PET scans, a dynamic approach was also used to quantify S₂ receptors in the frontal cortex of the baboon, which provided an estimate of receptor densityB _max =35.6 ± 10.9 pmol/g. The rate constants corresponding to transport into and out of tissue wereK _* ¹ = 0.2720 ± 0.0299 mol/min g andk _* ² = 0.0786 ± 0.0315 min^–1, respectively. The ligand-receptor dissociation constant wask _* ⁴ = 0.0154 ± 0.0109 min^–1.     

Alveolar echinococcosis of the liver: Diffusion-weighted MRI findings and potential role in lesion characterisation

Purpose

To report the diffusion-weighted MRI findings in alveolar echinococcosis (AE) of the liver and evaluate the potential role of apparent diffusion coefficients (ADCs) in the characterisation of lesions.

Materials and methods

We retrospectively included 22 patients with 63 AE liver lesions (≥1 cm), examined with 3-T liver MRI, including a free-breathing diffusion-weighted single-shot echo-planar imaging sequence (b-values = 50, 300 and 600 s/mm²). Two radiologists jointly assessed the following lesion features: size, location, presence of cystic and/or solid components (according to Kodama's classification system), relative contrast enhancement, and calcifications (on CT). The ADC_total, ADC_min and ADC_max were measured in each lesion and the surrounding liver parenchyma.

Results

Three type 1, 19 type 2, 17 type 3, three type 4 and 21 type 5 lesions were identified. The mean (±SD) ADC_total, ADC_min and ADC_max for all lesions were 1.73 ± 0.50, 0.76 ± 0.38 and 2.63 ± 0.76 × 10⁻³ mm²/s, respectively. The mean ADC_total for type 1, type 2, type 3, type 4 and type 5 lesions were 1.97 ± 1.01, 1.76 ± 0.53, 1.73 ± 0.41, 1.15 ± 0.42 and 1.76 ± 0.44 × 10⁻³ mm²/s, respectively. No significant differences were found between the five lesion types, except for type 4 (p = 0.0363). There was a significant correlation between the presence of a solid component and low ADC_min (r = 0.39, p = 0.0016), whereas an inverse correlation was found between the relative contrast enhancement and ADC_total (r = −0.34, p = 0.0072).

Conclusion

The ADCs of AE lesions are relatively low compared to other cystic liver lesions, which may help in the differential diagnosis. Although ADCs are of little use to distinguish between the five lesion types, their low value reflects the underlying solid component.