Correction to: Comparison of three-parameter kinetic model analysis to standard Patlak's analysis in 18F-FDG PET imaging of lung cancer patients.

Following publication of the original article [1], the authors flagged that the author affiliations detailed in the article are incorrect for the authors M. L. Calcagni and A. Giordano.

Comparison of three-parameter kinetic model analysis to standard Patlak's analysis in 18F-FDG PET imaging of lung cancer patients.

BACKGROUND: Patlak's graphical analysis can provide tracer net influx constant (Ki) with limitation of assuming irreversible tracer trapping, that is, release rate constant (kb) set to zero. We compared linear Patlak's analysis to non-linear three-compartment three-parameter kinetic model analysis (3P-KMA) providing Ki, kb, and fraction of free 18F-FDG in blood and interstitial volume (Vb). METHODS: Dynamic PET data of 21 lung cancer patients were retrospectively analyzed, yielding for each patient an 18F-FDG input function (IF) and a tissue time-activity curve. The former was fitted with a three-exponentially decreasing function, and the latter was fitted with an analytical formula involving the fitted IF data (11 data points, ranging 7.5-57.5 min post-injection). Bland-Altman analysis was used for Ki comparison between Patlak's analysis and 3P-KMA. Additionally, a three-compartment five-parameter KMA (5P-KMA) was implemented for comparison with Patlak's analysis and 3P-KMA. RESULTS: We found that 3P-KMA Ki was significantly greater than Patlak's Ki over the whole patient series, + 6.0% on average, with limits of agreement of ± 17.1% (95% confidence). Excluding 8 out of 21 patients with kb > 0 deleted this difference. A strong correlation was found between Ki ratio (=3P-KMA/Patlak) and kb (R = 0.801; P < 0.001). No significant difference in Ki was found between 3P-KMA versus 5P-KMA, and between 5P-KMA versus Patlak's analysis, with limits of agreement of ± 23.0 and ± 31.7% (95% confidence), respectively. CONCLUSIONS: Comparison between 3P-KMA and Patlak's analysis significantly showed that the latter underestimates Ki because it arbitrarily set kb to zero: the greater the kb value, the greater the Ki underestimation. This underestimation was not revealed when comparing 5P-KMA and Patlak's analysis. We suggest that further studies are warranted to investigate the 3P-KMA efficiency in various tissues showing greater 18F-FDG trapping reversibility than lung cancer lesions.

Estimating the amount of FDG uptake in physiological tissues.

INTRODUCTION: It is known that for a fixed amount of injected tracer, the amount available for a tissue of interest will be less if other tissues show intense uptake. The aim of this study was to estimate the magnitude of 2-deoxy-2-[(18)F]fluoro-D-glucose (18FDG) uptake amount in physiological tissues that may show an intense uptake in current clinical practice. METHODS: A formula was established providing an estimate of the percentage of injected 18FDG molecules (P; in %) that are irreversibly trapped in an 18FDG-positive tissue during a PET examination. RESULTS: P ≅ 0.17*exp(-λt(acq))*TLG/W, where λ is the (18)F physical decay constant, t(acq) is the injection-acquisition time delay, TLG is total lesion glycolysis (g) and W is the patient weight (kg). The magnitude of P was calculated in two patients showing an intense uptake in brown fat, myocardium and bowels: 0.5, 3.5, and 4.2% respectively. CONCLUSIONS: A formula is available to quickly estimate the amount of 18FDG uptake in tissues. We suggest that the accumulation of different physiological uptakes may actually affect SUV quantification in a tissue of interest.

Variability of average SUV from several hottest voxels is lower than that of SUVmax and SUVpeak.

OBJECTIVES: To assess variability of the average standard uptake value (SUV) computed by varying the number of hottest voxels within an (18)F-fluorodeoxyglucose ((18)F-FDG)-positive lesion. This SUV metric was compared with the maximal SUV (SUV(max): the hottest voxel) and peak SUV (SUV(peak): SUV(max) and its 26 neighbouring voxels). METHODS: Twelve lung cancer patients (20 lesions) were analysed using PET dynamic acquisition involving ten successive 2.5-min frames. In each frame and lesion, average SUV obtained from the N = 5, 10, 15, 20, 25 or 30 hottest voxels (SUV(max-N)), SUV(max) and SUV(peak) were assessed. The relative standard deviations (SDrs) from ten frames were calculated for each SUV metric and lesion, yielding the mean relative SD from 20 lesions for each SUV metric (SDr(N), SDr(max) and SDr(peak)), and hence relative measurement error and repeatability (MEr-R). RESULTS: For each N, SDr(N) was significantly lower than SDr(max) and SDr(peak). SDr(N) correlated strongly with N: 6.471 × N(-0.103) (r = 0.994; P < 0.01). MEr-R of SUV(max-30) was 8.94-12.63% (95% CL), versus 13.86-19.59% and 13.41-18.95% for SUV(max) and SUV(peak) respectively. CONCLUSIONS: Variability of SUV(max-N) is significantly lower than for SUV(max) and SUV(peak). Further prospective studies should be performed to determine the optimal total hottest volume, as voxel volume may depend on the PET system. KEY POINTS: • PET imaging provides functional parameters of (18) F-FDG-positive lesions, such as SUVmax and SUVpeak. • Averaging SUV from several hottest voxels (SUVmax-N) is a further SUV metric. • Variability of SUVmax-N is significantly lower than SUVmax and SUVpeak variability. • SUVmax-N should improve SUV accuracy for predicting outcome or assessing treatment response. • An optimal total hottest volume should be determined through further prospective studies.

[PET-CT in thoracic disease]. / TEP-TDM et thorax.

PET-CT imaging merges metabolic data obtained after injection of a tracer labelled with a positron emitter, with CT anatomical data. This whole-body technique provides (i) an improved spatial resolution and (ii) when the tracer is ¹8FDG, quantification of tissue glucose metabolism. In thoracic oncology, ¹8FDG PET-CT imaging allows diagnosis, staging, follow-up of treatment efficiency, and detection of recurrence. Furthermore, its potential usefulness in inflammatory and infectious diseases should be emphasized. Its main contra-indication is pregnancy, and a good knowledge of its technical procedure is mandatory. The most currently used quantification index is the standardized uptake value (SUV), whose interpretation requires caution.

[Pleural mesothelioma: imaging contribution]. / Le mésothéliome pleural: place de l'imagerie.

Imaging plays an essential role in management of patients of with pleural mesothelioma. In this article, we discuss the respective roles for ultrasonography, computed tomography, magnetic resonance imaging, and positon emission tomography for the diagnosis, staging, and postherapeutic evaluation of pleural mesothelioma.

Measurement of cardiac ventricular volumes using multidetector row computed tomography: comparison of two- and three-dimensional methods.

This study compared a three-dimensional volumetric threshold-based method to a two-dimensional Simpson's rule based short-axis multiplanar method for measuring right (RV) and left ventricular (LV) volumes, stroke volumes, and ejection fraction using electrocardiography-gated multidetector computed tomography (MDCT) data sets. End-diastolic volume (EDV) and end-systolic volume (ESV) of RV and LV were measured independently and blindly by two observers from contrast-enhanced MDCT images using commercial software in 18 patients. For RV and LV the three-dimensionally calculated EDV and ESV values were smaller than those provided by two-dimensional short axis (10%, 5%, 15% and 26% differences respectively). Agreement between the two methods was found for LV (EDV/ESV: r=0.974/0.910, ICC=0.905/0.890) but not for RV (r=0.882/0.930, ICC=0.663/0.544). Measurement errors were significant only for EDV of LV using the two-dimensional method. Similar reproducibility was found for LV measurements, but the three-dimensional method provided greater reproducibility for RV measurements than the two-dimensional. The threshold value supported three-dimensional method provides reproducible cardiac ventricular volume measurements, comparable to those obtained using the short-axis Simpson based method.

Noninvasive assessment of pulmonary arterial hypertension by MR phase-mapping method.

We describe a magnetic resonance (MR) imaging method that emphasizes pressure wave velocity to noninvasively assess pulmonary arterial hypertension. Both the blood flow and the corresponding vessel cross-sectional area (CSA) were measured by MR phase mapping in the main pulmonary artery (MPA) in 15 patients. MPA pressures were also measured, in the same patients, by right-side heart catheterization. Two significant relationships were established: 1) between the pressure wave velocity in the MPA and the mean pressure in the MPA (Ppa) writing pressure wave velocity = 9.25 Ppa - 202.51 (r = 0.82) and 2) between the ratio of pressure wave velocity to the systolic blood velocity peak in the MPA (R) and the mean pressure in the MPA writing R = 0.68 Ppa - 4.33 (r = 0.89). Using these relationships, we estimated two pressure values to frame the actual Ppa value in each patient from the present series with a reasonable reliability percentage (87%).

Feasibility of endocardial edge detection by using an inversion recovery artifact.

An inversion recovery (IR) artifact was used to delineate the blood/wall boundary in left ventricles. The artifact consisted of a hypointensity signal in pixels located at the boundary of two contiguous tissues with different T(1) relaxation times. The feasibility of measuring the ejection fraction using the artifact was tested in ten healthy volunteers, with two IR snapshot-FLASH sequences possessing different times of repetition (TR = 11msec and TR = 3.5msec) and appropriate times of inversion. The comparison with a cine-MRI sequence showed that ejection fraction measurements are feasible when performed with a snapshot-FLASH sequence that has a sufficiently short TR (3.5msec).

Tuning of pulmonary arterial circulation evidenced by MR phase mapping in healthy volunteers.

Magnetic resonance (MR) phase mapping was used to noninvasively assess both blood flow and cross-sectional area (CSA) in the main pulmonary artery (MPA) of 12 healthy volunteers. Flow and CSA patterns exhibited two positive peaks: high systolic and small diastolic. This finding can be explained using a simple "distributed" theoretical model that takes into account the role of a reflected pressure wave from pulmonary vascular impedance in generating a diastolic flow. The mean reflection coefficient of pressure wave, MPA input impedance, and pulmonary vascular impedance were assessed. We verified, in this series, that pressure wave velocity appears to be age-dependent. MR phase mapping has been used to observe the tuning (resonance) of the right cardiovascular system at rest under physiological conditions. MR phase mapping could be used to assess pathological modifications of the tuning that occurs in cases of pulmonary arterial hypertension.

Segmented 5 versus nonsegmented flow quantitation: comparison of portal vein flow measurements.

RATIONALE AND OBJECTIVES: Times of acquisition, mean velocities, mean flows, and their respective standard deviations provided by segmented and nonsegmented flow quantifications (FQ) were compared in the main portal veins of ten healthy adults. METHODS: The segmented FQ performed five phase-encoding lines per segment. The authors successively applied the two electrocardiogram-triggered techniques in the same slice perpendicular to the portal flow direction. Their measurements were compared in particular by means of the statistical analysis proposed by Bland and Altman. RESULTS: The segmented 5 FQ reduced the acquisition time by two compared with the nonsegmented FQ. The mean velocity and mean flow values of the two techniques were not significantly different. The standard deviations were similar. CONCLUSIONS: The segmented 5 FQ showed its major advantage in the portal vein: the acquisition time was reduced without any loss of accuracy or any uncertainty enhancement.

A validation of a flow quantification by MR phase mapping software.

AIM: We evaluated a Siemens software of flow quantification (FQ) by MR phase mapping, in the framework of a common practical use. METHODS: Experiments with a laminar flow phantom and in vivo pulsatile flow were performed. In particular, FQ in ascending aorta was investigated in healthy volunteers. RESULTS AND CONCLUSION: Flow phantom experiments reveal that the FQ slightly underestimates (8% on the average) actual velocities (mean velocities over a vessel area), and also that velocity uncertainties are related to the encoding velocity value, whatever the measured velocity. Furthermore, using well characterized working criteria, we found low intraobserver variability and negligible interobserver variability in ascending aorta FQs. The role played by the choice of reference area in FQ accuracy is emphasized. When recording several cardiac cycles during the same acquisition, it is shown that the FQ software may provide erroneous results. Several comments for FQ software use in the ascending aorta are added.

On the Deiters cell contribution to the micromechanics of the organ of Corti.

We give the first estimate of Young's modulus of the proteinaceous beam that makes the stiffness of the Deiters cell phalangeal processes. We show that the fundamental mode of vibration of an isolated phalanx is overdamped due to the damping imposed by the surrounding fluid. Then we consider the mechanical couplings that have so far been neglected in the micromechanics of the organ of Corti. Conclusions are drawn concerning the lack of significance of some expected resonant behaviour of isolated outer hair cells.

An improved technique for optical interferometric imaging of isolated cells.

We have improved the optical interferometric imaging technique that was recently used to measure local organic material concentrations in quasicylindrical cells. This allowed similar measurements for cells of arbitrary shape. The setup was used to measure the thickness of skin corneocytes.

Organic material concentration in auditory outer hair cells measured by laser interferometry.

Outer hair cells (OHC) of the mammalian cochlea are quasicylindrical cells of different length, which play a major role in hearing at threshold. Their particular shape allows the use of a noninvasive laser interferometric technique of isolated cells in vitro in order to measure the organic material concentration (OMC), hence the density of each cell body. In most (95%) of the OHCs isolated from the same guinea pig, when the cell diameter is normalized, the results show that the cell body OMC does not vary with cell length. In different animals, the respective normalized OMC mean values can vary between 70 kg/m3 and 103 kg/m3. A few OHCs with morphological particularities often possess cell body OMCs > 103 kg/m3. The results of the interferometric measurements in isolated OHCs confirm that density variations in the cell bodies are not involved in a sound frequency coding. The in vitro OMC variations of the OHCs could be related to the isolation procedure; however, they could also correlate with actual in vivo OMC variations.

Photo-released intracellular Ca2+ evokes reversible mechanical responses in supporting cells of the guinea-pig organ of Corti.

Loaded under whole cell patch-clamp configuration, the caged Ca2+ molecule DM-nitrophen was used to increase [Ca2+]i rapidly and reversibly in isolated Deiters cells of the organ of Corti. Photolysis of DM-nitrophen increased [Ca2+]i from resting concentrations of 20-50 nM to values above microM, as measured with the fluorescent indicator Fluo-3. Immediately after the photoliberation of Ca2+, a movement of the head of the phalangeal process could be observed in 75% of cells (n = 28). This mechanical movement, with an amplitude ranging between 0.5 to 1 micron within few hundred of ms, consisted of an extension of the phalanges away from the cell body. Measurement of phalangeal stiffness in transversal flexion toward the cell body ranged between 15-440 pN/micron. Stiffness can increase by 28 to 51% after rising [Ca2+]i. The results suggest Ca2+ as a potential intracellular messenger for active mechanical responses in Deiters cells.

Mammalian cochlear outer hair cells density evaluated by means of an optical tweezer.

We report on the first individual measurements of guinea pig's cochlear outer hair cells densities. Cells were isolated in vitro and manipulated with an optical tweezer. They were levitated in an upward laser beam coaxially trapping the cells. Then they were released by switching off the laser and let fall down in upright position. Measuring their speed and using the Stokes' law, we calculated their mean density. In our experimental frame, the results suggest that the density of the cellular body (between the basal nucleus and the apical cuticular plate) remains quasi constant whatever the cells' length. This implies that density variation of the cellular body does not participate in an intrinsic tuning mechanism.