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.

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.

The cardiosplenic axis: another obscure pathophysiological function of the spleen and its investigation using molecular imaging.

Splenic pathophysiology has been relatively unstudied, but recently, the spleen has received more attention as a result of the discovery of the 'cardiosplenic axis'. This term describes a role that the spleen plays in the progression of atherosclerosis following acute myocardial infarction. Human studies of this axis have largely used fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT to quantify peri-infarction inflammation, arterial wall inflammation and splenic metabolic activity. Most of these studies have quantified arterial wall inflammation and splenic metabolic activity using the standardized uptake value, but this is a semiquantitative measurement with several drawbacks, including overestimation of metabolic activity in overweight individuals and a dependence on blood glucose levels. A better approach to the measurement of metabolic activity using F-FDG is to measure tissue F-FDG clearance from dynamic imaging and Patlak-Rutland graphical analysis. This is the preferred approach for future human studies of the cardiosplenic axis that will be required to better define the nature of the spleen's role.