Stimulation of the hepatic arterial buffer response using exogenous adenosine: hepatic rest/stress perfusion imaging.

OBJECTIVES: The hepatic arterial buffer response is a mechanism mediated by adenosine whereby hepatic arterial perfusion (HAP) increases when portal flow decreases, and is implicated in liver disease. The first study aim was to measure HAP in patients undergoing myocardial perfusion imaging (MPI), thus developing hepatic arterial rest/stress perfusion imaging (HAPI). The second aim was to compare adenosine-induced changes in splenic perfusion (SP) and HAP with corresponding changes in myocardial blood flow (MBF). METHODS: Patients had MPI with 82Rb PET/CT using adenosine (n = 45) or regadenoson (n = 33) for stressing. SP and HAP were measured using a first-pass technique that gives HAP rather than total hepatic perfusion. Renal perfusion (RP) was also measured. RESULTS: Mean MBF and HAP increased after both adenosine ([stress-rest]/rest 1.1 and 0.8) and regadenoson (1.4 and 0.6), but the respective changes did not correlate. After adenosine, SP (- 0.48) and RP (- 0.26) both decreased. The change in SP correlated positively with the change in MBF (r = 0.36; p = 0.015) but did not correlate with change in HAP. After regadenoson, SP (0.2) and RP (0.2) both increased. The changes in SP correlated with the changes in MBF (r = 0.39; p = 0.025) and HAP (r = 0.39; p = 0.02). Changes in RP correlated with changes in HAP (r = 0.51; p = 0.0008) but not MBF. Resting SP (r = 0.32; p = 0.004), but not resting HAP, correlated with hepatic fat burden. Adenosine-induced change in HAP also correlated with hepatic fat (r = 0.29; p = 0.05). CONCLUSION: HAPI could be a useful new hepatic function test. Neither splenic 'switch-off' nor hepatic arterial 'switch-on' identifies adequacy of stress in MPI. KEY POINTS: • This article describes a new method for assessing arterial perfusion of the liver and its capacity to respond to an infusion of adenosine, a substance that normally 'drives' hepatic arterial flow. • Hepatic arterial flow increased in response to adenosine, sometimes dramatically. Adenosine is already used clinically to stimulate myocardial blood flow in patients with suspected coronary disease, but the increase in flow did not correlate with the corresponding increase in hepatic arterial flow. • Analogous to the use of adenosine in the myocardium, the increase in hepatic arterial flow in response to adenosine has the potential to be a new clinically useful method for the evaluation of hepatic arterial haemodynamics in liver disease.

Effect of blood glucose level on standardized uptake value (SUV) in 18F- FDG PET-scan: a systematic review and meta-analysis of 20,807 individual SUV measurements.

OBJECTIVES: To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in 18F-FDG-PET scan. METHODS: A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, 18F-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (< 110, 110-125, 125-150, 150-200, and > 200 mg/dl). RESULTS: Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p < 0.001, p < 0.001,) and muscle (p < 0.001, p < 0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p = 0.008, p < 0.001). No significant correlation was found between BGL and SUVmax or SUVmean in tumors. In the ANOVA test, all hyperglycemic groups had significantly lower SUVs compared with the euglycemic group in brain and muscle, and significantly higher SUVs in liver and blood pool. However, in tumors only the hyperglycemic group with BGL of > 200 mg/dl had significantly lower SUVmax. CONCLUSION: If BGL is lower than 200 mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.

Lymphatic drainage efficiency: a new parameter of lymphatic function.

Background Following convection from blood capillaries, plasma proteins are transported to loco-regional lymph nodes in two stages: first, uptake into peripheral lymphatics, and second, transport to nodes. Purpose To introduce a new parameter of lymphatic function that quantifies stage 2 - lymphatic drainage efficiency (LDE). Material and Methods Percentage injected activity (IIQ) in ilio-inguinal nodes 150 min following subcutaneous foot web-space injection of Tc-99 m-nanocolloid was measured in 102 patients undergoing lymphoscintigraphy using a method in which a standard is placed by image guidance over the nodes. Percentage activity leaving the injection depot by 150 min ( k) was measured in 60/102 patients. LDE (%) = 100 × (IIQ/ k). Abnormal lymphoscintigraphy was defined qualitatively as: (i) no activity in ilio-inguinal nodes at 45 min or negligible activity at 150 min (delay); (ii) lymph diversion through skin and/or deep system; and (iii) focal tracer accumulation suggesting cellulitis. Results Scintigraphy was bilaterally normal in 82 limbs, unilaterally normal in 40 limbs and abnormal in 82 limbs. IIQ correlated with k in bilaterally normal (r = 0.86; n = 52), unilaterally normal (r = 0.67; n = 27), and abnormal (r = 0.82; n = 41) limbs. IIQ, k, and LDE were significantly lower in unilaterally normal (9.3 ± 5.4%, 13.8 ± 7.1%, and 65 ± 30%) compared with bilaterally normal limbs (15.4 ± 8.4% [ P > 0.0001], 18.3 ± 8.9% [ P = 0.025], and 84 ± 30% [ P = 0.01]). LDE was lower in limbs displaying skin diversion and/or delay. Conclusion LDE is a new quantitative index that has potential value in clinical research but requires further clinical evaluation. Abnormal quantitative indices indicate that limbs unilaterally normal on lymphoscintigraphy are not functionally normal.

Quantification of tumour (18) F-FDG uptake: Normalise to blood glucose or scale to liver uptake?

PURPOSE: To compare normalisation to blood glucose (BG) with scaling to hepatic uptake for quantification of tumour (18) F-FDG uptake using the brain as a surrogate for tumours. METHODS: Standardised uptake value (SUV) was measured over the liver, cerebellum, basal ganglia, and frontal cortex in 304 patients undergoing (18) F-FDG PET/CT. The relationship between brain FDG clearance and SUV was theoretically defined. RESULTS: Brain SUV decreased exponentially with BG, with similar constants between cerebellum, basal ganglia, and frontal cortex (0.099-0.119 mmol/l(-1)) and similar to values for tumours estimated from the literature. Liver SUV, however, correlated positively with BG. Brain-to-liver SUV ratio therefore showed an inverse correlation with BG, well-fitted with a hyperbolic function (R = 0.83), as theoretically predicted. Brain SUV normalised to BG (nSUV) displayed a nonlinear correlation with BG (R = 0.55); however, as theoretically predicted, brain nSUV/liver SUV showed almost no correlation with BG. Correction of brain SUV using BG raised to an exponential power of 0.099 mmol/l(-1) also eliminated the correlation between brain SUV and BG. CONCLUSION: Brain SUV continues to correlate with BG after normalisation to BG. Likewise, liver SUV is unsuitable as a reference for tumour FDG uptake. Brain SUV divided by liver SUV, however, shows minimal dependence on BG. KEY POINTS: • FDG standard uptake value in tumours helps clinicians assess response to treatment. • SUV is influenced by blood glucose; normalisation to blood glucose is recommended. • An alternative approach is to scale tumour SUV to liver SUV. • The brain used as a tumour surrogate shows that neither approach is valid. • Applying both approaches, however, appropriately corrects for blood glucose.

Accumulation of (18)F-FDG in the liver in hepatic steatosis.

OBJECTIVE: Nonalcoholic fatty liver disease is associated with hepatic inflammation. An emerging technique to image inflammation is PET using the glucose tracer, (18)F-FDG. The purpose of this study was to determine whether in hepatic steatosis the liver accumulates FDG in excess of FDG physiologically exchanging between blood and hepatocyte. MATERIALS AND METHODS: Hepatic FDG uptake, as SUV = [voxel counts / administered activity] × body weight), and CT density were measured in a liver region in images obtained 60 minutes after injection of FDG in 304 patients referred for routine PET/CT. Maximum SUV (region voxel with the highest count rate, SUVmax) and average SUV ( SUVave) were measured. Blood FDG concentration was measured as the maximum SUV over the left ventricular cavity (SUVLV). SUVave was adjusted for hepatic fat using a formula equating percentage fat to CT density. Patients were divided in subgroups on the basis of blood glucose (< 4, 4 to < 5, 5 to < 6, 6 to < 8, 8 to < 10, and > 10 mmol/L). Hepatic steatosis was defined as CT density less than 40 HU (n = 71). RESULTS: The percentage of hepatic fat increased exponentially with blood glucose. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV but not SUVave / SUVLV correlated with blood glucose. Fat-adjusted SUVave was higher in patients with hepatic steatosis (p < 0.001) by ~0.4 in all blood glucose groups. There was a similar difference (~0.3) in SUVmax (p < 0.005) but no difference in SUVave. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV correlated with blood glucose in patients with hepatic steatosis but not in those without. SUVave / SUVLV correlated with blood glucose in neither group. CONCLUSION: FDG uptake is increased in hepatic steatosis, probably resulting from irreversible uptake in inflammatory cells superimposed on reversible hepatocyte uptake.

Implantation of the coronary sinus reducer for refractory angina due to coronary microvascular dysfunction in the context of apical hypertrophic cardiomyopathy-a case report.

Background: Refractory angina leads to a poor quality of life and increased healthcare resource utilization. In this growing population of patients, multiple mechanism(s) of ischaemia may co-exist, including functional disorders of the coronary microcirculation. There are few evidence-based effective therapies resulting in a large unmet clinical need. Case summary: A 38-year-old woman with refractory angina was referred with daily chest pain despite multiple anti-anginal medications and previous percutaneous coronary intervention. Cardiac magnetic resonance imaging demonstrated apical hypertrophic cardiomyopathy (HCM). Rubidium-82 positron emission tomography (PET) with regadenoson stress confirmed significant myocardial ischaemia in the apex and apical regions (16% of total myocardium) with a global myocardial perfusion reserve (MPR) of 1.23. Coronary angiography confirmed patent stents and no epicardial coronary artery disease. Therefore, the mechanism of ischaemia was thought attributable to coronary microvascular dysfunction (CMD) in the context of HCM. In view of her significant symptoms and large burden of left-sided myocardial ischaemia, a Coronary Sinus Reducer (CSR) was implanted. Repeat PET imaging at 6 months showed a marked reduction in ischaemia (<5% burden), improvement in global MPR (1.58), symptoms, and quality of life. Conclusion: In refractory angina, ischaemia may be due to disorders of both the epicardial and coronary microcirculations. The CSR is a potential therapy for these patients, but its mechanism of action has not been confirmed. This report suggests that CSR implantation may reduce myocardial ischaemia and improve symptoms by acting on the coronary microcirculation. The efficacy of CSR in patients with CMD and its mechanism of action on the coronary microcirculation warrant further investigation.

82 Rb tissue kinetics in humans.

AIM: The study aim was to compare the kinetics of the potassium analogue, 82 Rb, between spleen, liver and kidney. METHODS: Patients had myocardial stress/rest perfusion imaging using adenosine (n = 45) or regadenoson (n = 33) for stressing. Hepatic arterial (HAP), splenic (SP) and renal (RP) perfusions were measured from first-pass and blood 82 Rb clearances (Ki) from Gjedde-Patlak-Rutland graphical analysis of data between 1 and 2 min postinjection, using regions of interest over left ventricular cavity or abdominal aorta to monitor arterial concentration. Tissue 82 Rb extraction efficiency (E) was calculated as [Ki/perfusion]*100. Tissue extracellular fluid volume (ECV) was derived from the GPR plot intercept. RESULTS: SP (24%) and RP (23%) increased after regadenoson but decreased (-41% and -19%) after adenosine. HAP increased after adenosine (91%) and regadenoson (68%). Resting E was high in kidney (69%) and low in spleen (26%). After adenosine, it increased to 91% in kidney and 49% in spleen. Assuming an arterial contribution of 25% to hepatic blood flow, resting E in liver was estimated as 23%. Relationships between Ki and perfusion in spleen and kidney were consistent with the Crone-Renkin equation (Ki = [1 - A.e-B/perfusion ]*perfusion), with respective values of A of 0.95 and 0.94 and B of 31 and 186 ml/min/100 ml. Splenic ECV decreased following adenosine from 62 to 39 ml/100 ml and showed a logarithmic correlation with SP. CONCLUSION: Kidney, spleen and liver display contrasting tissue kinetics. E is high in kidney and low in spleen and liver. Spleen is erectile, collapsing when perfusion decreases.

Measuring myocardial blood flow with 82rubidium using Gjedde-Patlak-Rutland graphical analysis.

OBJECTIVE: Myocardial blood flow (MBF) is measured with 82Rb using non-linear, least-squares computerised modelling. The study aim was to explore the feasibility of Gjedde-Patlak-Rutland (GPR) graphical analysis as a simpler method for measuring MBF. METHODS: Patients had myocardial perfusion imaging using adenosine (n = 45) or regadenoson (n = 33) for stressing. Blood 82Rb clearance into myocytes (K1) was measured from Cedar-Sinai QPET software using the modified Crone-Renkin equation of Lortie et al. (K1 = [1-0.77 × e-B/MBF] × MBF) to convert K1 to MBF (ml/min/100 ml), where B (63 ml/min/100 ml) is myocardial permeability-surface area product. Using aorta or left ventricular cavity (LV) to measure arterial blood 82Rb concentration, blood 82Rb clearance into myocardium (Z) was measured from GPR analysis based on data acquired between 1 and 3 min post-injection. As units of K1 and Z are, respectively, ml/min/ml intracellular space and ml/min/ml total tissue including extracellular space, myocardial extracellular fluid volume (ECV) is 1 - [Z/K1]. Using Z/K1 (see Results) to modify its index, the Lortie equation was changed to Z = (1-0.77 × [Formula: see text]e-BZ/MBFZ)*MBFZ, following which MBFZ was calculated from Z. In GPR analysis, spillover of activity from LV to myocardium conveniently 'drops out' in the intercept of the plot. RESULTS: Both agents increased myocardial blood flow almost equally. ECV was ~ 35 ml/100 ml at rest, increasing to ~ 40 ml/100 ml after stress. Z/K1, averaged between stress, rest, stressing agents and arterial ROI, was 0.62, so BZ was taken as 39 (i.e. 0.62 × 63) ml/min/100 ml. Based on LV, MBFZ (y) correlated with MBF (x): y = 0.43x + 22 ml/min/100 ml; r = 0.84; n = 156). Their respective stress/rest ratios showed a moderate correlation (r = 0.64; n = 78). CONCLUSIONS: GPR analysis offers promise as a valid and analytically simpler technique for measuring myocardial blood flow, which, as with any clearance measured from GPR analysis, has units of ml/min/ml total tissue volume, and merits development as a polar map display.

FDG PET/CT of the non-malignant liver in an increasingly obese world population.

Because of obesity, non-alcoholic fatty liver disease (NAFLD) is becoming increasingly important. 10% of NAFLD patients develop non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and is now the leading indication for liver transplantation in the Western world. Prefibrotic NASH can only be reliably diagnosed by biopsy. However, given its success in other inflammatory diseases, PET/CT with 18 F-fluorodeoxyglucose (FDG), although non-specific, may offer a promising approach to diagnosing not only NASH but also other inflammatory liver conditions. In addition, FDG PET has generated pathophysiological information on hepatic glucose metabolism and, diagnostically, used liver for quantification of tumour FDG accumulation (e.g. Deauville scoring). A review of hepatic FDG PET is therefore timely. There are two general approaches to the quantification of hepatic FDG accumulation: firstly, standard uptake value (SUV) and secondly dynamic PET. SUV is a poor index of hepatic metabolic function because most hepatic FDG (~75%) is un-phosphorylated 60-min postinjection. Hepatic fat is increased in NAFLD but accumulates negligible FDG. Because fat distribution is heterogeneous, maximum pixel SUV is therefore preferred to mean pixel SUV. Computer modelling of dynamic PET dissects the transport constants governing hepatic FDG kinetics but is challenged by the liver's dual blood supply. Graphical analysis is less informative but more robust and will be the preferred clinical approach to measurement of hepatic FDG phosphorylation. Previous dynamic PET studies have ignored hepatic fat and therefore potentially underestimated glucose accumulation in patients with hepatic steatosis. Future work should use graphical analysis of dynamic PET and correction for hepatic fat.

Hepatic and splenic 18 F-FDG blood clearance rates (Ki) in hepatic steatosis and diabetes mellitus.

AIM: The study aim was to investigate the relationships of blood glucose level (BGL) with hepatic and splenic blood FDG clearances (Ki) in patients with diabetes mellitus (DM) and/or hepatic steatosis (HS). METHODS: This was a retrospective study of 238 patients, including 92 with type 2 DM (DM2) and 11 with type 1 DM (DM1), having routine whole body FDG PET/CT. Patients with lymphoma were excluded. Patients were divided into the following groups: HS-DM-, HS-DM2+, HS+DM-, HS+DM2+ and 2 DM1 groups (hypoglycaemic and hyperglycaemic). ROI were placed over liver and spleen for measurement of SUVmax , and left ventricular cavity (LV) for measurement of SUVmean . Tissue SUVmax was divided by LV SUVmean . This division, giving Z, eliminates bias from the whole body metric used to calculate SUV and renders SUVmax a closer surrogate of Ki. HS was diagnosed when hepatic unenhanced CT was ≤40 HU. RESULTS: In all patients, individual hepatic Z and individual splenic Z correlated significantly with individual BGL. Highest mean hepatic Z and highest mean BGL were recorded in HS+ DM2+ group and lowest in hypoglycaemic DM1 group. Patients with DM1 and hyperglycaemia showed low hepatic Z in relation to BGL. Hepatic and splenic Z correlated inversely with CT density in patients without DM but not in those with DM2. CONCLUSION: As BGL increases, hepatocyte glucokinase is up-regulated. This includes patients with HS and DM2 but not DM1. We speculate that in HS and DM2, up-regulation results from insulin resistance and hyperinsulinaemia. The data also support a hepato-splenic metabolic axis.

99mTc-MAG3 Diuretic Renography: Intra- and Inter-Observer Repeatability in the Assessment of Renal Function.

The aim of the present study is to evaluate the intra- and inter-observer agreement in assessing the renal function by means of 99mTc-MAG3 diuretic renography. One hundred and twenty adults were enrolled in the study. One experienced and one junior radiographer processed the renograms twice by assigning manual and semi-automated regions of interest. The differential renal function (DRF, %), time to maximum counts for the right and left kidney (TmaxR-TmaxL, min) and time to half-peak counts (T1/2, min) were calculated. The Bland-Altman analysis (bias±95% limits of agreement), Lin's concordance correlation coefficient and weighted Fleiss' kappa coefficient were used to assess agreement. Based on the Bland-Altman analysis, the intra-observer repeatability results for the experienced radiographer using the manual and the semi-automated techniques were 0.2 ± 2.6% and 0.3 ± 6.4% (DRF), respectively, -0.01 ± 0.24 and 0.00 ± 0.34 (TmaxR), respectively, and 0.00 ± 0.26 and 0.00 ± 0.33 (TmaxL), respectively. For the junior radiographer, the respective results were 0.5 ± 5.0% and 0.8 ± 9.4% (DRF), 0.00 ± 0.44 and 0.01 ± 0.28 (TmaxR), and 0.01 ± 0.28 and -0.02 ± 0.44 (TmaxL). The inter-observer repeatability for the manual method was 0.6 ± 5.0% (DRF), -0.10 ± 0.42 (TmaxR) and -0.05 ± 0.38 (TmaxL), and for the semi-automated method -0.2 ± 9.1% (DRF), 0.00 ± 0.31 (TmaxR) and -0.05 ± 0.40 (TmaxL). The weighted Fleiss' kappa coefficient for the T1/2 assessments ranged between 0.85-0.97 for both intra- and inter-observer repeatability with both methods. These findings suggest a very good repeatability in DRF assessment with the manual method-especially for the experienced observer-but a less good repeatability with the semi-automated approach. The calculation of Tmax was also operator-dependent. We conclude that reader experience is important in the calculation of renal parameters. We therefore encourage reader training in renal scintigraphy. Moreover, the manual tool seems to perform better than the semi-automated tool. Thus, we encourage cautious use of automated tools and adjunct validation by manual methods where possible.

Tissue standardized uptake value is a closer surrogate of blood fluorine-18 fluorodeoxyglucose clearance after division by blood standardized uptake value, illustrated in brain and liver.

The numerator and denominator of the left-hand side of the Gjedde-Patlak-Rutland (GPR) equation for measurement of blood fluorine-18 fluorodeoxyglucose (F-FDG) clearance into tissue (Ki) are the standardized uptake values (SUVs) of tissue and blood, respectively. The extent to which normalized time (NT) in the GPR equation exceeds real time depends on half-time of clearance of F-FDG from blood. A literature review shows that NT is fairly constant, about 100 min at 60 min postinjection of F-FDG, in keeping with our own finding of no significant difference in maximum SUV in blood 60 min postinjection of F-FDG between 39 patients with F-FDG-avid malignancy on routine PET/CT (1.74±0.31) and 21 patients with normal PET/CT (1.79±0.32), and similar blood glucose levels (BGLs). Volume of distribution (V0) in the GPR equation is ∼0.4 ml/ml for brain and ∼0.9 ml/ml for lean liver. Using these values of V0 and an NT of 100 min, we used the GPR equation to calculate Ki from our own published values of SUVliver/SUVblood and SUVbrain/SUVblood at 60 min postinjection, obtaining 0.0045 ml/min/ml for liver and 0.036 ml/min/ml for brain at BGL of 5 mmol/l. These values for Ki at this BGL are close to literature values of Ki, which for liver and brain are ∼0.0033 and ∼0.035 ml/min/ml, respectively. We conclude, therefore, that following division with blood pool SUV, tissue SUV becomes a closer surrogate of Ki. This division also eliminates the controversy over which whole body metric to use in the calculation of SUV.

The appropriate whole body metric for calculating standardised uptake value and the influence of sex.

AIM: To compare weight, lean body mass and body surface area for calculation of standardised uptake value (SUV) in fluorine-18-fluorodeoxyglucose PET/computed tomography, taking sex into account. PATIENTS AND METHODS: This was a retrospective study of 161 (97 men) patients. Maximum standardised uptake value (SUVmax) and mean standardised uptake value (SUVmean) were obtained from a 3-cm region of interest over the right lobe of the liver and scaled to weight, scaled to lean body mass (SUL) and scaled to body surface area (SUA). Mean hepatic computed tomography density was used to adjust SUVmean for hepatic fat (SUVFA). Hepatic SUV indices were divided by SUV from left ventricular cavity, thereby, eliminating whole body metric, to obtain a surrogate of blood fluorine-18-fluorodeoxyglucose clearance into liver, and multiplied by blood glucose to give a surrogate of hepatic glucose uptake rate (mSUV). RESULTS: SULmax, SUAmax and all scaled to weight indices correlated strongly with weight. SULmean, SULFA, SUAmean and SUAFA, however, correlated weakly or not at all with weight, nor with their corresponding whole body metric in men or women, but correlated strongly when the sexes were combined into one group. This was the result of sex differences in SUL (greater in men) and SUA (greater in women). There was, however, no sex difference in mSUV. CONCLUSION: Weight is unsuitable for calculating SUV. SUL and SUA are also inappropriate as maxima but appropriate as mean and fat-adjusted values. However, SUL is recommended for both sexes because SUA is influenced by both body fat and weight. Sex differences in SUL and SUA give rise to misleading correlations when sexes are combined into one group.

Intrahepatic fluorine-18-fluorodeoxyglucose kinetics measured by least squares nonlinear computer modelling and Gjedde-Patlak-Rutland graphical analysis.

We aimed to use simple physiological equations to show similarities and differences in blood fluorine-18-fluorodeoxyglucose (F-FDG) clearance in the liver (Ki) and distribution volume (V0) in the liver, respectively, generated from nonlinear least squares computer modelling and Gjedde-Patlak-Rutland graphical analysis of dynamic F-FDG PET. We show theoretically that when, as is usually the case, vascular fraction (fraction of liver occupied by blood, Vb) is included as a parameter in modelling but ignored in graphical analysis, the ratio of Ki values, respectively, generated by graphical anlaysis (Ki) and by modelling (Ki) is equal to 1-Vb. This theoretical prediction was then confirmed from dynamic PET data acquired in a clinical population of patients undergoing routine F-FDG PET/computed tomography and from a review of the literature in which it can be seen that Ki/Ki ranges from 0.47 to 0.98. When Vb is not included as a parameter in modelling, Ki is theoretically equal to Ki and to V0·k3, and V0 is equal to V0. There are several attractions to normalising Ki to V0 with respect to liver. Thus, first, there is no need to correct imaging for photon attenuation. Second, it makes no difference whether uptake constant is expressed as blood or plasma clearance. Third, it circumvents the effects of hepatic fat, which, because it accumulates negligible F-FDG, physically dilutes the F-FDG signal and reduces both uptake constant and distribution volume.

Relationship between regional hepatic glucose metabolism and regional distribution of hepatic fat.

AIM: Hepatic steatosis is associated with insulin resistance and hyperinsulinaemia. Insulin stimulates hepatic glucokinase, even in insulin resistance, so hepatic glucose uptake is increased in hepatic steatosis. The study hypothesis was that hepatic glucose uptake is also influenced locally by fat, the hepatic distribution of which is heterogeneous. PATIENTS AND METHODS: Sixty patients undergoing PET/CT using fluorine-18-fluorodeoxyglucose (F-FDG) had dynamic imaging of the liver for 30 min after injection before undergoing whole-body PET/CT at 60 min after injection. Hepatic F-FDG uptake was measured using Gjedde-Patlak-Rutland graphical analysis. Plot gradient (Ki), which represents hepatic blood clearance of F-FDG to phosphorylation, was normalized to intercept [V(0)], which represents the hepatic F-FDG distribution volume. The 60 min computed tomography (CT) was co-registered on to each of the 30 dynamic PET frames. This failed in 20 patients. A further seven patients with lymphoma and three with hepatic metastases were excluded. Within transaxial sections, the liver was divided into small regions of interest (ROIs) of 5×5 pixels each in sections of 5 mm (range: 118-586 ROIs/liver). CT density and Ki/V(0) were measured in each ROI. RESULTS: Throughout the 25-pixel ROIs in the individual liver, CT density and Ki/V(0) showed a significant negative correlation in 15/30 patients. It was significantly positive in only three (P=0.01). In some patients, parametric imaging showed regional concordance between Ki/V(0) and hepatic fat, identified as reduced CT density. CONCLUSION: In addition to systemic influences, hepatic glucose uptake is regionally linked to the distribution of hepatic fat. Increased metabolism could be the cause or result of local fat deposition.

A case of fever of unknown origin: (18)F-FDG-PET/CT findings in Takayasu's arteritis.

This is a case of a 54 years old woman with fever of unknown origin. Physical examination showed nothing remarkable. Chest radiographs, abdominal ultrasound examination (US) and chest-abdominal-pelvic CT, showed segmental thickening of the wall of the aorta. On admission, the C-reactive protein level and the erythrocyte sedimentation rate were elevated. (18)Fluoro-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET/CT) showed increased uptake of the aorta wall and its main branches that could be indicative of arteritis. The temporal artery biopsy was negative for giant-cell arteritis. The patient responded well to prednisolone treatment. A second (18)F-FDG-PET/CT scan showed great improvement. (18)F-FDG-PET/CT scan early indicates arteritis of the great vessels that in this case was considered to be TA and contributes in monitoring disease activity.

Hepato-splenic axis: hepatic and splenic metabolic activities are linked.

The concept of a hepato-splenic axis has recently been put forward. We aimed to investigate whether hepatic and splenic metabolic activities are linked, and if splenic metabolic activity is increased in non-alcoholic fatty liver disease (NAFLD). Blood clearance rates of phosphorylated 18F-fluorodeoxyglucose were measured in the spleen and liver from dynamic PET using Gjedde-Patlak-Rutland graphical analysis and abdominal aorta for input function in 59 patients undergoing routine PET/CT. Plot gradient (Ki), which represents blood clearance, was divided by intercept (V(0)), which represents tissue FDG distribution volume, and multiplied by blood glucose to give glucose uptake rate per unit tracer distribution volume (MRglu). In addition, liver-to-spleen raw count rate ratio was plotted against time, and gradient (b) divided by intercept (A) to obtain hepatic-to-splenic blood clearance ratio independent of aortic input function. Hepatic steatosis was inferred when hepatic CT density was ≤40 HU. There was no difference in splenic MRglu between 8 patients with inactive lympho-proliferative disease (LPD) as identified by negative PET/CT, 25 with non-haematological malignancy and 13 with normal PET/CT. It was significantly increased in 13 with active LPD, who were therefore excluded, along with 3 more with type-2 diabetes mellitus. Splenic MRglu was higher in patients with hepatic steatosis (4.0±1.6; n = 12) than without (2.6±1.7 µmol/min/100 ml; P = 0.02) and correlated inversely with hepatic CT density (r = -0.49; P<0.001). Hepatic and splenic Ki/V(0) correlated (r = 0.52; P<0.01) in 22 patients in whom the correlation coefficient between b/A and hepatic-to-splenic Ki/V(0) ratio was 0.99 and in whom, therefore, input function errors in graphical analysis could be discounted. In men, splenic longitudinal diameter correlated significantly with hepatic CT density (r = -0.35; P = 0.046), hepatic MRglu (r = 0.44; P = 0.005) and splenic MRglu (r = 0.35; P = 0.046). Splenic Ki/V(0) correlated positively with blood glucose, suggesting sensitivity to insulin. We conclude that hepatic and splenic metabolic activities are linked and that a speculative mechanism, which deserves further investigation, is shared insulin sensitivity. Splenic MRglu and spleen size are increased in NAFLD.