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Purpose: To study blood flow (BF) and metabolism in normal pancreas and in different pancreatic lesions. We then determined the effect of these biomarkers on outcome in patients with pancreatic cancer.Experimental Design: Oxygen-15–labeled water and fluorodeoxyglucose positron emission tomography/computed tomography scans were used in 26 patients with a suspicion of pancreatic cancer to measure pancreatic BF and metabolism. In addition, the ratio of standardized uptake value to BF (SUV/BF) was calculated. Patients were divided into three groups: patients with a finding of normal pancreas (n = 7), benign lesions (n = 8), and malignant tumors (n = 11).Results: Patients with benign and malignant pancreatic tumors had decreased BF of the lesion by 48% and 60%, respectively, compared with patients with normal pancreatic tissue. SUVmax was 3-fold higher in malignant tumors compared with both benign lesions and normal pancreas (P < 0.05). In contrast, the SUVmax of patients with benign lesions and normal pancreas did not differ. The SUV/BF ratio was significantly higher in malignant lesions than in benign lesions or in patients with normal pancreas (P < 0.05). In patients with cancer, high SUV/BF ratio was a stronger predictor of poor survival compared with high metabolism or lower-than-normal pancreatic BF.Conclusions: BF in pancreatic cancer is significantly reduced compared with the normal pancreas, which may in part explain the poor success of both radiotherapy and chemotherapy. We suggest that the composite measurement of BF and metabolism in pancreatic cancer could serve as a novel tool in the planning of treatments targeting vasculature. (Clin Cancer Res 2009;15(17):5511–7)

CCR Translation for the Article from Decreased Blood Flow with Increased Metabolic Activity: A Novel Sign of Pancreatic Tumor Aggressiveness

LUMA-keskus Saimaan KEY-kehityshankkeessa koululaiset tutustuvat kiviin, energiaan ja ympäristöön. Minä Vaikuttaja! – osuus innostaa ottamaan haltuun kestävän kehityksen periaatteita ja toimintatapoja. Yläkoululaiset herätellään pohtimaan omia valintojaan ja tekemään arjessa pieniä valintoja kestävän kehityksen puolesta. Harjoitukset on jaoteltu kahteen teemaan: energian säästäminen ja vastuullinen kuluttaminen. Kiehtovat kivet – osuudessa innostetaan perehtymään kiviin ja kivialaan. Osuudessa toteutetaan kaksi erilaista kaupunkisuunnistusta kohderyhminä esi- ja alkuopetsu sekä yläkoulun 9.luokka. Kaupunkisuunnistus tutustuttaa koululaisia kivien maailmaan, tuo näkyväksi kiven käyttöä mm. rakennusmateriaalina ja kertoo kivialan ammateista.

BACKGROUND Only a small fraction of patients with atherosclerotic renovascular disease (ARVD) treated with revascularization have improved renal function after the procedure. It has been suggested that this may be due to effects of renal microvascular disease. Our aim was to measure the effect of renal artery stenosis (RAS) revascularization on renal perfusion in patients with renovascular disease. METHODS Seventeen renovascular disease patients were treated by dilatation of unilateral (N = 8) or bilateral (N = 9) RAS (N = 23 kidneys), mainly because of uncontrolled or refractory hypertension. The patients were studied before and after (103 ± 29 days) the procedure. Renal perfusion was measured using quantitative positron emission tomography (PET) perfusion imaging. RESULTS Although renal perfusion correlated inversely with the degree of RAS in patients with renovascular disease, it did not change after revascularization. CONCLUSIONS Our data support the notion of former clinical trials that angiographic severity of RAS does not determine the response to revascularization. Quantitative PET perfusion imaging is a promising tool to noninvasively measure renal perfusion for the assessment of physiological impact of RAS.

Previous human studies have shown divergent results concerning the effects of exercise training on myocardial blood flow (MBF) at rest or during adenosine-induced hyperaemia in humans. We studied whether these responses are related to alterations in adenosine A2A receptor (A2AR) density in the left-ventricular (LV) myocardium, size and work output of the athlete's heart, or to fitness level. MBF at baseline and during intravenous adenosine infusion, and A2AR density at baseline were measured using positron emission tomography, and by a novel A2AR tracer in 10 healthy male endurance athletes (ET) and 10 healthy untrained (UT) men. Structural LV parameters were measured with echocardiography. LV mass index was 71% higher in ET than UT (193 ± 18 g m−2versus 114 ± 13 g m−2, respectively). MBF per gram of tissue was significantly lower in the ET than UT at baseline, but this was only partly explained by reduced LV work load since MBF corrected for LV work was higher in ET than UT, as well as total MBF. The MBF during adenosine-induced hyperaemia was reduced in ET compared to UT, and the fitter the athlete was, the lower was adenosine-induced MBF. A2AR density was not different between the groups and was not coupled to resting or adenosine-mediated MBF. The novel findings of the present study show that the adaptations in the heart of highly trained endurance athletes lead to relative myocardial ‘overperfusion’ at rest. On the other hand hyperaemic perfusion is reduced, but is not explained by A2AR density.

Subcutaneous adipose tissue blood flow is finely regulated, and tuned with fat metabolism; little is known about visceral fat, which is less accessible in humans. In estimating blood flow with positron emission tomography (PET) and oxygen-15-labelled water (( 15 O)H2O), the input function is obtained invasively from arterial blood samples. The aim of the current study was to validate a non-invasive method to measure blood flow in adipose depots, by extracting input function curves from ( 15 O)H2O-PET images. Data of twenty subjects undergoing abdominal ( 15 O)H2O-PET were used. Images were reconstructed with filtered backprojection (FBP). Location, diameter, and inner radioactivity levels of the abdominal aorta were automatically determined. Image derived arterial curves (IDI) were compared to measured arterial blood data, as obtained by an online blood sampler (OSI). Blood flow in three adipose tissue depots was estimated using the autoradiographic method with OSI vs the FBP image derived input (F-IDI) function. Correlations between blood flow results obtained with OSI and IDI were significant (r 0.87, p

Purpose: To study blood flow (BF) and metabolism in normal pancreas and in different pancreatic lesions. We then determined the effect of these biomarkers on outcome in patients with pancreatic cancer. Experimental Design: Oxygen-15–labeled water and fluorodeoxyglucose positron emission tomography/computed tomography scans were used in 26 patients with a suspicion of pancreatic cancer to measure pancreatic BF and metabolism. In addition, the ratio of standardized uptake value to BF (SUV/BF) was calculated. Patients were divided into three groups: patients with a finding of normal pancreas (n = 7), benign lesions (n = 8), and malignant tumors (n = 11). Results: Patients with benign and malignant pancreatic tumors had decreased BF of the lesion by 48% and 60%, respectively, compared with patients with normal pancreatic tissue. SUVmax was 3-fold higher in malignant tumors compared with both benign lesions and normal pancreas (P < 0.05). In contrast, the SUVmax of patients with benign lesions and normal pancreas did not differ. The SUV/BF ratio was significantly higher in malignant lesions than in benign lesions or in patients with normal pancreas (P < 0.05). In patients with cancer, high SUV/BF ratio was a stronger predictor of poor survival compared with high metabolism or lower-than-normal pancreatic BF. Conclusions: BF in pancreatic cancer is significantly reduced compared with the normal pancreas, which may in part explain the poor success of both radiotherapy and chemotherapy. We suggest that the composite measurement of BF and metabolism in pancreatic cancer could serve as a novel tool in the planning of treatments targeting vasculature. (Clin Cancer Res 2009;15(17):5511–7)

Previous human studies have shown divergent results concerning the effects of exercise training on myocardial blood flow (MBF) at rest or during adenosine-induced hyperaemia in humans. We studied whether these responses are related to alterations in adenosine A2A receptor (A2AR) density in the left-ventricular (LV) myocardium, size and work output of the athlete's heart, or to fitness level. MBF at baseline and during intravenous adenosine infusion, and A2AR density at baseline were measured using positron emission tomography, and by a novel A(2A)R tracer in 10 healthy male endurance athletes (ET) and 10 healthy untrained (UT) men. Structural LV parameters were measured with echocardiography. LV mass index was 71% higher in ET than UT (193 +/- 18 g m(-2) versus 114 +/- 13 g m(-2), respectively). MBF per gram of tissue was significantly lower in the ET than UT at baseline, but this was only partly explained by reduced LV work load since MBF corrected for LV work was higher in ET than UT, as well as total MBF. The MBF during adenosine-induced hyperaemia was reduced in ET compared to UT, and the fitter the athlete was, the lower was adenosine-induced MBF. A2AR density was not different between the groups and was not coupled to resting or adenosine-mediated MBF. The novel findings of the present study show that the adaptations in the heart of highly trained endurance athletes lead to relative myocardial 'overperfusion' at rest. On the other hand hyperaemic perfusion is reduced, but is not explained by A2AR density.

The quantitative assessment of renal blood flow (RBF) may help to understand the physiological basis of kidney function and allow an evaluation of pathophysiological events leading to vascular damage, such as renal arterial stenosis and chronic allograft nephropathy. The RBF may be quantified using PET with H(2)(15)O, although RBF studies that have been performed without theoretical evaluation have assumed the partition coefficient of water (p, ml/g) to be uniform over the whole region of renal tissue, and/or radioactivity from the vascular space (V(A). ml/ml) to be negligible. The aim of this study was to develop a method for calculating parametric images of RBF (K(1), k(2)) as well as V(A) without fixing the partition coefficient by the basis function method (BFM).The feasibility was tested in healthy subjects. A simulation study was performed to evaluate error sensitivities for possible error sources.The experimental study showed that the quantitative accuracy of the present method was consistent with nonlinear least-squares fitting, i.e. K(1,BFM)=0.93K(1,NLF)-0.11 ml/min/g (r=0.80, p0.001), k(2,BFM)=0.96k(2,NLF)-0.13 ml/min/g (r=0.77, p0.001), and V(A,BFM)=0.92V(A,NLF)-0.00 ml/ml (r=0.97, p0.001). Values of the Akaike information criterion from this fitting were the smallest for all subjects except two. The quality of parametric images obtained was acceptable.The simulation study suggested that delay and dispersion time constants should be estimated within an accuracy of 2 s. V(A) and p cannot be neglected or fixed, and reliable measurement of even relative RBF values requires that V(A) is fitted. This study showed the feasibility of measurement of RBF using PET with H(2)(15)O.