Andrea Lupi

The effect of 18F-FDG-PET/CT respiratory gating on detected metabolic activity in lung lesions

ObjectiveRespiratory gated PET/CT (positron emission tomography/computed tomography) of the lung is expected to increase the accuracy of quantitative determinations in lesional activities, regardless of the gating method used; reasonably, respiratory gating should increase standard uptake value (SUV; and possibly decrease lesional size), on the basis of the reduction of the “smearing effect.” However, literature data are very limited, particularly for in vivo studies. The objective of this article is to test the SUV variations in a large group of lung lesion studies.MethodsA group of 26 consecutive positive studies (21 men, 5 women, age 36-84, mean 68), performed on patients referred to our institution for known or suspected lung cancer, are examined. All studies were performed both with conventional PET/CT total body scan and with Real-Time Position Management (RPM) triggered selective gated study of the thorax. Four studies were considered technically unsatisfactory and were discarded; the remaining 22 studies are the object of this work. Max lesional SUVs were evaluated in both settings by semi-automated algorithms; for the gated studies, both values of the bin that showed more relevant variations from the clinical routinary study (“best bin”) and an average value that was calculated over all bins were determined. Results were compared on a one-to-one basis.ResultsIn conventional, SUV showed a mean ± standard deviation (SD) value of 9.2 ± 6.9 (range 0.9–26). In the averaged gated studies, the mean ± SD value was 13.4 ± 11.7 (range 1.4–47); in the “best bin” dataset the mean ± SD was 14.9 ± 12.9, ranging from 1.6 to 53.1. In general, the use of respiratory trigger induced rather variable but overall consistent increases in SUV. If the percentage variations in the average trigger dataset are considered, there is an average increase of +60%, SD ± 97 (P < 0.05). Similar results are found in the “best bin” dataset, the average percentage increase in SUV values being +77.2% (SD ± 04.6).ConclusionsIn lung cancer, triggering procedures increase the signal to noise ratio. The increase in SUV determined by gating is very variable, but generally relevant. This could lead to an SUV values cut-off revision, and may have an impact on smaller lesions detection.

A New Semiempirical Mathematical Model for Prediction of Internal Filtration in Hollow Fiber Hemodialyzers

The potential of convective solute transport for blood purification has been widely explored. New techniques (such as hemodiafiltration), based on a combination of diffusion and convection techniques, have been developed. Owing to the internal filtration/backfiltration (IF/BF) phenomenon, high-flux dialysis also relies on a convective component, which, however, is hard to quantify and thus optimize. In this work, we developed a mathematical model designed to supply the clinician with a quantification of the IF/BF fluxes taking place during high-flux dialysis. IF fluxes are predicted based on the machine settings and blood hematocrit/protein concentration. The hydraulic characteristics of commercial dialyzers were derived from bloodless bench tests. Moreover, an in vitro blood test was conducted on a 1.8 m2 polysulfone dialyzer using an established scintigraphic analysis, for verification of model prediction accuracy. Results of simulations show that the IF/BF rate is sensitive to the blood flow rate and (to a lesser extent) to the dialysate flow rate. Increasing net ultrafiltration rates resulted in parallel increases of direct filtration and simultaneous decreases of BF. IF/BF is rather influenced by blood composition, due to the complex dependence of oncotic pressure and blood viscosity upon hematocrit and plasma protein concentration. Simulation results showed an excellent agreement with the experimental results obtained with scintigraphy, with only a 3% prediction error. With respect to some previous works, this model is simpler in its theoretical approach. It allows implementation into a user-friendly software tool and might be used to predict the convective component in high-flux dialysis and possibly to optimize it.

Cerebellar vermis relative hypermetabolism: an almost constant PET finding in an injured brain.

Cortical alterations of brain metabolism, as seen in PET, obviously depend on the nature of the damage (either mechanical, toxic, anoxic, or other). However, some subcortical abnormalities seem to occur rather frequently regardless of the extension, position and cause of the damage. In particular, relative cerebellar vermis activation seems to be frequently encountered. The aim of this work was to determine the incidence of this pattern in a heterogeneous population of brain trauma, and to compare it on a quantitative basis with a group of age-sex matched controls. The case records of this study consist of 58 consecutive patients, 44 males, 14 females, age 14–69 (median 34) 44 traumatic, 8 anoxic, 4 vascular and 2 toxic injuries. In the trauma group, the visualization of the cerebellar vermis was readily appreciable as a consistent majority of cases. In particular, the mean vermis/cerebellum ratio (calculated by appropriate ROI positioning) was 1.26 ± 0.17 SD (range 0.92–1.82); in the control group the same parameters showed much less dispersion: average 0.92 ± 0.06, range 0.80–1.10 (P < 0.005). If, on the basis of the normal group data, a cut-off value of 1 is accepted for the v/c ratio, it is noted that 54/57 trauma patients (95%) showed a ratio above this value. In conclusion, a hypermetabolic cerebellar vermis is a common finding in a damaged brain, regardless of the nature of the trauma (probably due to the relative preservation compared with other structures of alternative metabolic pathways), and seems to be the hallmark of the injured brain.

Heart-Kidney Biomarkers in Patients Undergoing Cardiac Stress Testing

We examined association of inducible myocardial perfusion defects with cardiorenal biomarkers, and of diminished left ventricular ejection fraction (LVEF) with kidney injury marker plasma neutrophil gelatinase-associated lipocalin (NGAL). Patients undergoing nuclear myocardial perfusion stress imaging were divided into 2 groups. Biomarkers were analyzed pre- and poststress testing. Compared to the patients in the low ischemia group (n = 16), the patients in the high ischemia group (n = 18) demonstrated a significantly greater rise in cardiac biomarkers plasma BNP, NT-proBNP and cTnI. Subjects were also categorized based on pre- or poststress test detectable plasma NGAL. With stress, the group with no detectable NGAL had a segmental defect score 4.2 compared to 8.2 (P = .06) in the detectable NGAL group, and 0.9 vs. 3.8 (P = .03) at rest. BNP rose with stress to a greater degree in patients with detectable NGAL (10.2 vs. 3.5 pg/mL, P = .03). LVEF at rest and with stress was significantly lower in the detectable NGAL group; 55.8 versus 65.0 (P = .03) and 55.1 vs. 63.8 (P = .04), respectively. Myocardial perfusion defects associate with biomarkers of cardiac stress, and detectable plasma NGAL with significantly lower LVEF, suggesting a specific heart-kidney link.

Relative Hypermetabolism of Vermis Cerebelli in Traumatic Brain Injured Patients Studied with 18FDG PET: A Descriptor of Brain Damage and a Possible Predictor of Outcome

PURPOSE The almost constant presence of apparent metabolic hypermetabolism of cerebellar vermis seen on 18FDG PET in a population of injured brains has been reported in a previous paper. Aim of this paper is to determine a) whether there is a correlation between the entity of this sign, semi quantitatively determined, and the severity of the trauma at its onset, and b) whether the entity of the relative enhancement correlates with the medium and long term clinical outcome. METHODS A group of 45 consecutive patients admitted to the Acquired Brain Injury Unit of our Hospital for recent, major head trauma, underwent a basal 18FDG PET/CT scan of the brain; the presence of relative hypermetabolism of the vermis cerebelli was visually assessed and semi quantitatively determined (vermis/cerebellum ratio: V/C); the median V/C value was used as a divide between low V/C ratios (group A) and high V/C ratios (group B). During one year after trauma, every patient from both groups received an extensive testing to evaluate cognitive and behavioral performances and evolution: Disability Rating Scale (DRS) and Levels of Cognitive Function (LCF) were administered monthly from month 1 to month 6, and at 12 months from the trauma; Glasgow Outcome Scale (GOS) was administered at 3, 6 and 12 months from the head trauma. Numerical scores from each of these performance-testing protocols were cross-matched with values derived from the V/C 18FDG PET/CT determinations. A relative risk estimate via Chi-square testing was performed on the results of both groups for LCF and DRS scales at 1, 6 and 12 months from trauma. RESULTS At one month after trauma, overall LCF (LCF1) values ranged from 2 to 8, avg. 3.77, SD ± 2.10; the average value in group A was 5.21, SD ± 2.09, in B group 2.47, SD ± 0.98 (F=17.5, P = 0). At this time, overall average DRS (DRS1) was 6.7, SD ± 2.05, ranging from 2 to 9; the average value was 5.52, SD ± 0.47 in group A, and 7.72, SD ± 0.30 in group B (F = 6.3, P = 0.01). Relative risk estimates for patients with higher V/C ratios for poor performance in DRS scale were: 2.46 at 1 month (confidence boundaries 1.66 - 3.64), 3.75 (c.b. 1.64 - 8.64) at 6 months, 5.17 (c.b. 1.76 - 15.16) at one year. Relative risk estimates for LCF scale were: 3.20 (c.b. 1.74 - 5.90) at 1 month, 6.909 (c.b. 1.03 - 46.15) at 6 months, 4.22 (c.b. 0.65 - 27.10) at 12 months. CONCLUSIONS A) there is a strong correlation between the semi quantitatively determined values of vermian relative hypermetabolism and the severity of trauma as determined by standard cognitive and performance testings; the V/C ratio may therefore be considered a reliable, although non-specific, index of brain suffering. B) there is a good statistical correlation between the semi quantitative vermian/cerebellar ratio determined shortly after the trauma, and the clinical outcome of the patients, evaluated by standard clinical performance tests and relative risk estimates.

Quantification of Internal Filtration in Hollow Fiber Hemodialyzers with Medium Cut-Off Membrane

Background: Inadequate removal of molecules between 5 and 50 KDa may cause long-term complication in chronic hemodialysis. Medium cut-off (MCO) is a new class of membranes with enhanced sieving properties and negligible albumin loss. MCO membrane makes it possible to perform expanded hemodialysis (HDx), a technique based on high internal filtration (IF).The present study is designed to quantify IF in 2 MCO dialyzers (Theranova 400 and 500, Baxter, Deerfield, USA) using a nuclear imaging technique previously validated. Methods: Blood and dialysate compartment pressure drop along with transmembrane pressure; they were measured in a closed in vitro circuit with human blood (blood flow [QB] = 300 and 400 mL/min; dialysate flow 500 mL/min; net ultrafiltration rate 0 mL/min). A non-diffusible marker molecule (albumin macro-aggregates labeled with 99Tc metastable) was injected in the blood compartment and nuclear emission was recorded by a gamma camera. Relative variations in the concentration of the marker molecule along the length of the filter were used to calculate local cross filtration. Results: Based on marker concentration profiles, IF was estimated. For Theranova 400, IF were 29.7 and 41.6 mL/min for QB of 300 and 400 mL/min. For Theranova 500, IF were 31.6 and 53.1 mL/min for QB of 300 and 400 mL/min respectively. Conclusions: MCO membrane provides significant amounts of IF due to the particular combination between hydraulic permeability of the membrane and reduced inner diameter of the fibers. High IF combined with enhanced sieving profile of MCO membrane leads to improved removal of a wider spectrum of uremia retention molecules in HDx, without requiring complex equipment.

Pre-therapy hyperfunctioning follicular thyroid carcinoma evaluation with I-131 whole-body scan and with F-18 FDG PET/CT.

We describe a patient with persistent hyperthyroidism after total thyroidectomy for toxic multinodular goiter and without therapy with levothyroxine evaluated with I-131 whole-body scan and with F-18 FDG PET/CT scan. Scintigraphy performed 48 hours after radiopharmaceutical administration showed many areas of focal radioiodine uptake. A week later we performed a PET/CT scan to better localize the anatomic site of the iodine-positive lesions. Both scans, performed after methimazole withdrawal, visualized the same lesions, and these results were used as a guide for biopsy. Histologic examination was consistent with metastatic follicular thyroid carcinoma.