Quality assessment of fluorodeoxyglucose positron emission tomography imaging in clinical setting: definition of standard quality control parameters for patients treated for lymphoma.

PURPOSE: We designed standard parameters for quality controls (QCs) of F-fluorodeoxyglucose positron emission tomography (FDG PET) images in the clinical setting, and validated them in both cross-sectional and longitudinal cohorts of patients with lymphoma under treatment. METHODS: The procedure is based on the measurement of mean standardized uptake value (SUV mean) in three specific regions of interest drawn within pulmonary, liver, and bone tissues [reference (Ref)]. Intraobserver and interobserver reproducibility [percentage of coefficient of variation (CV%)] were calculated using PET scans of healthy participants. Cross-sectional interpatient QCs were defined as the 95% ranges of normal values of Ref-SUV mean. Transversal QCs were applied on PET scans of patients treated for lymphoma (n=378) looking at Ref-SUV mean out of range. Longitudinal intrapatient QCs were defined as the 95% limits of the SUV mean variation between two consecutive scans (ΔSUV limits). Longitudinal QCs were applied in a group of 94 pairs of consecutive PET scans under treatment for lymphoma looking at patients having Ref-ΔSUV limits out of range. RESULTS: Intraobserver CV% remained below 3%, whereas interobserver CV% was a maximum of 5.3%. Both in transversal and longitudinal cohorts of patients treated for lymphoma, none of the PET scans simultaneously showed the three Ref-SUV mean out of range. Similar results were obtained with ΔSUV limits. Situations in which these limits were exeeded were associated with a recent history of acute infectious pulmonary disease (lung tissues) and granulocytes colony-stimulating factors concomitant treatment and stimulation of bone marrow (bone tissues). CONCLUSION: A standardized and reproducible FDG PET QC protocol using SUV mean measurements using three tissues of Ref was validated, and may be applied in the clinical setting or in a clinical trial.

Organ segmentation with level sets using local shape and appearance priors.

Organ segmentation is a challenging problem on which recent progress has been made by incorporation of local image statistics that model the heterogeneity of structures outside of an organ of interest. However, most of these methods rely on landmark based segmentation, which has certain drawbacks. We propose to perform organ segmentation with a novel level set algorithm that incorporates local statistics via a highly efficient point tracking mechanism. Specifically, we compile statistics on these tracked points to allow for a local intensity profile outside of the contour and to allow for a local surface area penalty, which allows us to capture fine detail where it is expected. The local intensity and curvature models are learned through landmarks automatically embedded on the surface of the training shapes. We use Parzen windows to model the internal organ intensities as one distribution since this is sufficient for most organs. In addition, since the method is based on level sets, we are able to naturally take advantage of recent work on global shape regularization. We show state-of-the-art results on the challenging problems of liver and kidney segmentation.

Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate.

OBJECTIVE: Our objective was to analyze the relationship between bone mineral density (BMD) changes and fracture incidence during 3-yr treatment with strontium ranelate. PATIENTS: Women from the strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention study and the TReatment Of Peripheral OSteoporosis study were evaluated. OUTCOME MEASURES: The outcome measures included BMD at the lumbar spine, femoral neck, and total proximal femur assessed at baseline and after a follow-up of 1 and 3 yr; semiquantitative visual assessment of vertebral fractures; and nonvertebral fractures based on written documentation. RESULTS: After 3 yr of strontium ranelate treatment, each percentage point increase in femoral neck and total proximal femur BMD was associated with a 3% (95% adjusted confidence interval, 1-5%) and 2% (1-4%) reduction in risk of a new vertebral fracture, respectively. The 3-yr changes in femoral neck and total proximal femur BMD explained 76% and 74%, respectively, of the reduction in vertebral fractures observed during the treatment. Three-year changes in spine BMD were not statistically associated with the incidence of new vertebral fracture (P = 0.10). No significant associations were found between 3-yr changes in BMD and incidence of new nonvertebral fractures, but a trend was found for femoral neck BMD (P = 0.09) and for total proximal femur BMD (P = 0.07). An increase in femoral neck BMD after 1 yr was significantly associated with the reduction in incidence of new vertebral fractures observed after 3 yr (P = 0.04). CONCLUSION: During 3-yr strontium ranelate treatment, an increase in femoral neck BMD was associated with a proportional reduction in vertebral fracture incidence.

Direct evidence of the temperature dependence of Gd-BOPTA transport in the intact rat liver.

The aim was to study the influence of temperature on the transport of the hepatobiliary contrast agent Gadobenate dimeglumine (Gd-BOPTA). Rat livers were isolated and perfused with Gd-BOPTA at 12, 25, 30, 36 and 38 degrees C. After the perfusion period, biopsies were collected and the MR signal intensity was measured. Uptake and biliary excretion were quantified with radiolabeled Gd-BOPTA. MR signal intensity decreased with temperature of perfusion. This phenomenon was appropriately quantified with 153Gd and 153Sm labeling, in contrast to 67Ga.

Comparison of fat-free mass and body fat in Swiss and American adults.

OBJECTIVE: No current studies have compared North American with European body composition parameters, i.e., fat-free mass (FFM), body fat (BF), and percentage of BF (%BF) in large populations. This study compared FFM, BF, and %BF values derived from two bioelectrical impedance analysis (BIA) equations (Geneva and National Health and Nutrition Examination Survey [NHANES]) in Swiss subjects and compared FFM, BF, and %BF values of white Swiss with those of white North American adults with the same BIA equations. METHODS: Healthy adults (3714 men and 3199 women), ages 20 to 79 y, in Switzerland were measured by single-frequency BIA and compared with means and standard deviations for body mass index and body composition parameters obtained from the NHANES III study (United States; n = 2538 men, 2862 women). FFM was calculated with the Geneva and NHANES equations. RESULTS: Mean FFMGENEVA values did not differ from FFMNHANES values in men but was significantly lower (-1.5 kg) in women. FFM and BF values in American men, who weighed 4.2 to 12.0 kg more than the Swiss men, were significantly higher (+2.1 to +6.0 kg and +1.5 to +6.4 kg, respectively) than those in the Swiss men. FFM and BF values in American women, who weighed 2.3 to 12.1 kg more than the Swiss women, were significantly higher (+1.3 to +2.1 kg and +4.8 to +11.8 kg, respectively, except FFM in subjects ages 20 to 29 y and BF in those ages 70 to 79 y) than FFMGENEVA values in Swiss women. FFM in American women was significantly lower (+1.3 and +1.9 kg) and non-significantly higher than FFMNHANES in Swiss women. CONCLUSION: NHANES and Geneva BIA equations estimate body composition equally well in men, but further research is necessary to determine the discrepancies in FFM between BIA equations in women. The greater weight of the American subjects yielded higher values for FFM, BF, and %BF in American than in Swiss men and women.

Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18F]fluoro-2-deoxy-D-glucose.

PURPOSE: Tumor uptake of 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) may relate to outcome in cancer patients. Pretreatment FDG uptake was evaluated as a predictor of local control (LC) and disease-free survival (DFS) in patients with head-and-neck cancer managed primarily either by radiotherapy (RT) or surgery. PATIENTS AND METHODS: Tumor FDG uptake using the Standardized Uptake Value (SUV) was measured in 120 patients studied prospectively using positron emission tomography (PET). Treatment consisted of either radical RT with or without chemotherapy (73 patients) or radical surgery with or without postoperative RT (47 patients). Median follow-up of the surviving patients was 48 months. RESULTS: The median SUV was higher in 46 patients who failed treatment than in the remaining controlled patients (5.8 vs. 3.6, p = 0.002). In monovariate analysis, patients with tumors having high FDG uptake (SUV > median, 4.76) had poorer LC (p = 0.003) and DFS (p = 0.005). This difference was also observed when the RT and surgery groups were analyzed separately. In the multivariate analysis T-category (p = 0.005) and SUV (p = 0.046) remained independent adverse factors for LC, whereas N-category (p = 0.004), T-category (p = 0.02) and SUV (p = 0.05) were independent determinants of DFS. CONCLUSION: These results suggest that pretreatment tumor FDG uptake represents an independent prognostic factor in patients with head-and-neck cancers, whatever the primary treatment modality. Tumors having high FDG uptake are at greater risk of failure and should be considered for more aggressive multimodality therapy.

Aging, physical activity and height-normalized body composition parameters.

BACKGROUND & AIM: Regular physical activity prevents or limits weight gain, and gain in body mass index (BMI) and decreases mortality. The aims of the study in healthy adults were to determine the differences in fat-free mass index (FFMI) (kg/m(2)) and body fat mass index (BFMI) between age groups and determine the association between physical activity and FFMI and BFMI. METHODS: Caucasian men (n=3549) and women (n=3184) between 18 and 98 years, were classified as either sedentary or physically active (at least 3h per week at moderate or high-intensity level activity). FFMI and BFMI were measured by 50 kHz bioelectrical impedance analysis. RESULTS: BFMI was significantly higher (P<0.05) in sedentary than physically active subjects and the differences became progressively greater with age. The physically active subjects were significantly less likely to have a low or high FFMI (logistic regression, P<0.001), and a high or very high BFMI (P<0.001), and more likely to have low BFMI (P<0.001) compared to sedentary adults. In contrast with fat-free mass, which was lower in older subjects, the height-normalized FFMI was stable with age until 74 years and lower thereafter. Significantly higher BFMIs were noted in older subjects. CONCLUSION: Physically active subjects are less likely to have low or high FFMI, and high or very high BFMI, and more likely to have low BFMI. In contrast to common claim that fat-free mass decreases with age, we found that FFMI was stable until 74 years. The use of FFMI and BFMI permits comparison of subjects with different heights and age.

Attenuation compensation in cerebral 3D PET: effect of the attenuation map on absolute and relative quantitation.

It is generally well accepted that transmission (TX)-based non-uniform attenuation correction can supply more accurate absolute quantification; however, whether it provides additional benefits in routine clinical diagnosis based on qualitative interpretation of 3D brain positron emission tomography (PET) images is still the subject of debate. The aim of this study was to compare the effect of the two major classes of method for determining the attenuation map, i.e. uniform versus non-uniform, using clinical studies based on qualitative assessment as well as absolute and relative quantitative volume of interest-based analysis. We investigated the effect of six different methods for determining the patient-specific attenuation map. The first method, referred to as the uniform fit-ellipse method (UFEM), approximates the outline of the head by an ellipse assuming a constant linear attenuation factor (mu=0.096 cm(-1)) for soft tissue. The second, referred to as the automated contour detection method (ACDM), estimates the outline of the head from the emission sinogram. Attenuation of the skull is accounted for by assuming a constant uniform skull thickness (0.45 cm) within the estimated shape and the correct micro value (0.151 cm(-1)) is used. The usual measured transmission method using caesium-137 single-photon sources was used without (MTM) and with segmentation of the TX data (STM). These techniques were finally compared with the segmented magnetic resonance imaging method (SMM) and an implementation of the inferring attenuation distributions method (IADM) based on the digital Zubal head atlas. Several image quality parameters were compared, including absolute and relative quantification indexes, and the correlation between them was checked. The qualitative evaluation showed no significant differences between the different attenuation correction techniques as assessed by expert physicians, with the exception of ACDM, which generated artefacts in the upper edges of the head. The mean squared error between the different attenuation maps was also larger when using this latter method owing to the fact that the current implementation of the method significantly overestimated the head contours on the external slices. Correlation between the mean regional cerebral glucose metabolism (rCGM) values obtained with the various attenuation correction methods and those obtained with the gold standard (MTM) was good, except in the case of ACDM (R(2)=0.54). The STM and SMM methods showed the best correlation (R(2)=0.90) and the regression lines agreed well with the line of identity. Relative differences in mean rCGM values were in general less than 8%. Nevertheless, ANOVA results showed statistically significant differences between the different methods for some regions of the brain. It is concluded that the attenuation map influences both absolute and relative quantitation in cerebral 3D PET. Transmission-less attenuation correction results in a reduced radiation dose and makes a dramatic difference in acquisition time, allowing increased patient throughput.

Assessment of the impact of model-based scatter correction on [18F]-FDG 3D brain PET in healthy subjects using statistical parametric mapping.

It is recognized that scatter correction can supply more accurate absolute quantification, and that iterative reconstruction results in better noise properties and significantly reduces streak artefacts; however, it is not entirely clear whether they produce significant changes in [18F]-FDG distribution of reconstructed 3D brain PET images relative to not scatter corrected images and analytic reconstruction procedures. The current study assesses the effect of model-based scatter correction using the single-scatter simulation algorithm and iterative reconstruction in 3D brain PET studies, using statistical parametric mapping (SPM) analysis. The study population consisted of 14 healthy volunteers (6 males, 8 females; age 63-80 years). PET images were reconstructed using an analytic 3DRP reprojection algorithm with (SC) and without explicit scatter correction (NSC), as well as using an iterative ordered subset-expectation maximization (OSEM) algorithm. Calculated attenuation correction was performed assuming uniform attenuation (mu = 0.096 cm(-1)) for brain tissues when data are precorrected for scatter. The broad-beam attenuation coefficient (mu = 0.06 cm(-1)) determined from phantom studies was applied to NSC images. The images were coregistered and normalized using the default [15O]-H2O template supplied with SPM99 and an [18F]-FDG template. A t statistic image for the contrast condition effect was then constructed. The contrast comparing SC to NSC images suggest that regional brain metabolic activity decreases significantly in the frontal gyri, in addition to the middle temporal and postcentral gyri. On the other hand, activity increases in the cerebellum, thalamus, insula, brainstem, temporal lobe, and the frontal cortex. No significant changes were detected when comparing images reconstructed using analytic and iterative algorithms. It is concluded that, for some cerebral areas, significant differences in [18F]-FDG distribution arise when images are reconstructed with and without explicit SC. This needs to be considered when interpreting [18F]-FDG 3D brain PET images after applying SC.

Hip fracture discrimination study: QUS of the radius and the calcaneum.

As an emerging alternative to current radiation-based bone densitometry techniques, there is a growing interest in the use of quantitative ultrasound (QUS) measurements for the noninvasive assessment of fracture risk in the management of osteoporosis. However, there are also a multiplicity of technologically different QUS devices available on the market and, so far, no study has compared heel and radius QUS device for the discrimination of subjects with hip fractures. Our study evaluated the ability of three QUS devices (one calcaneal gel-coupled system, one calcaneal water-coupled system, and one radius system) to discriminate osteoporotic from controls subjects, using the same population. We also checked if the combination of two different skeletal sites (i.e., calcaneum and radius) improve the discriminatory ability of the QUS devices. Forty-five women aged 79.1+/-7.1 yr with hip fractures within the last 4 d were used as the hip-fracture group and compared to 40 healthy controls from 65-87 yr. In addition, 47 young controls, aged 20-40 yr, were used as reference population to express some of the results as T-scores. QUS measurements were performed with the Hologic Sahara, Ge-Lunar Achilles+, and Sunlight Omnisense devices according to the manufacturer's recommendations. Adjusted odds ratio results showed that a decrease in Omnisense SOS of 1 standard deviation (SD) was associated with a significant increase in fracture risk (OR adj.=2.83) comparable with Sahara BUA (OR adj.=2.42) and Achilles BUA (OR adj.=3.29). However, given the large overlap between the 95% intervals of each odds ratio, no significant difference was found between the devices. Similarly, comparison between the areas under ROC curves did not show any significant difference between all the parameters. Considering the parameters provided per default by each QUS device, the Sahara, Achilles, and Omnisense devices classified correctly 70, 67.5, and 62.5% of the subjects, respectively. Although the OR of the combination of radius and calcaneum is improved (3.62 to 4.74) compared with either one of the single skeletal site, the large confidence intervals do not allow to claim a significant difference. The three QUS technologies tested against hip fractures seem to show the same discriminatory ability. However, there is some differences in the definition of the diagnostic threshold underlying the nonusability of the World Health Organization (WHO) osteoporosis definition. Finally the combination of several site using two different devices is not clinically relevant. Potential interest could be seen in combining several sites using the same device, supposing that such device would measure differently active bone.

Magnetic resonance imaging-guided attenuation and scatter corrections in three-dimensional brain positron emission tomography.

Reliable attenuation correction represents an essential component of the long chain of modules required for the reconstruction of artifact-free, quantitative brain positron emission tomography (PET) images. In this work we demonstrate the proof of principle of segmented magnetic resonance imaging (MRI)-guided attenuation and scatter corrections in three-dimensional (3D) brain PET. We have developed a method for attenuation correction based on registered T1-weighted MRI, eliminating the need of an additional transmission (TX) scan. The MR images were realigned to preliminary reconstructions of PET data using an automatic algorithm and then segmented by means of a fuzzy clustering technique which identifies tissues of significantly different density and composition. The voxels belonging to different regions were classified into air, skull, brain tissue and nasal sinuses. These voxels were then assigned theoretical tissue-dependent attenuation coefficients as reported in the ICRU 44 report followed by Gaussian smoothing and addition of a good statistics bed image. The MRI-derived attenuation map was then forward projected to generate attenuation correction factors (ACFs) to be used for correcting the emission (EM) data. The method was evaluated and validated on 10 patient data where TX and MRI brain images were available. Qualitative and quantitative assessment of differences between TX-guided and segmented MRI-guided 3D reconstructions were performed by visual assessment and by estimating parameters of clinical interest. The results indicated a small but noticeable improvement in image quality as a consequence of the reduction of noise propagation from TX into EM data. Considering the difficulties associated with preinjection TX-based attenuation correction and the limitations of current calculated attenuation correction, MRI-based attenuation correction in 3D brain PET would likely be the method of choice for the foreseeable future as a second best approach in a busy nuclear medicine center and could be applied to other functional brain imaging modalities such as SPECT.

Four-year follow-up of body compostion in lung transplant patients.

BACKGROUND: Both undernutrition and overnutrition can affect the quality of life and survival of patients with pulmonary disease and lead to quantitative and functional alterations of fat-free mass (FFM). This longitudinal study determines the changes in weight, FFM, and body fat before and up to 4 years after lung transplant (LTR). METHODS: Height, weight, and body composition measurements (bioelectrical impedance) were obtained in 37 LTR patients. FFM and body fat were measured before and at 1, 3, 6, 9, 12, 18, 24, 36, and 48 months after LTR. RESULTS: Weight changed by +16.6%, +3.2%, -0.2%, and -3.2% and FFM by +14.0%, +2.5%, -0.3%, and -1.0% during years 1, 2, 3, and 4, respectively. A diagnosis of obliterative bronchiolitis after LTR was associated with loss of body weight, FFM, and body fat, compared with stable weight or gain in weight, FFM, and body fat in obliterative bronchiolitis-negative subjects; 76.2% and 85.7%, and 28% and 38% of men and women, respectively, demonstrated low FFM at 1 month and at 2 years after LTR, respectively. The FFM change was higher (39% of weight) during year 1 than during year 2 (25%) or year 3 (21%). CONCLUSIONS: After LTR, patients gained weight, FFM, and body fat, and two-thirds reached normal levels of FFM by year 2. A weight increase resulted in an FFM increase. Contrary to studies after heart or liver transplantation, our results suggest that despite posttransplant infections and grafts rejection, LTR permits FFM recovery.

[New brain imaging techniques]. / Les nouvelles techniques d'imagerie du cerveau.

Neuroimaging technologies have improved neurology and neurosurgery by providing tools to look inside the brain and investigate its functions and diseases. As for any tool, the users should know the basics of each technique and be aware about their uses and limitations. Here we review these new techniques and illustrate their use with examples from studies at the University Hospital in Geneva. From all the techniques, MRI (Magnetic Resonance Imagery) has the highest spatial resolution. Taking advantage of the magnetic properties of the hydrogen nucleus, it is possible to reach a sub-millimeter resolution in 3D. When MRI images are digitized, they can be treated to perform re-slicing, segmentation and 3D reconstruction of cortical surfaces, as well as to measure anatomical structures (volumetry). Functional MRI (fMRI) is based on blood oxygenation changes when a task is performed or when epileptic activity occurred. Then it can be used to non-invasively show for example language, motor or epileptic network activation. Electromagnetic imaging techniques, based on EEG and MEG, have the power to localize in 3D the electrical activity of the brain with millisecond temporal resolution and then to follow the temporal activation of neuronal networks. These techniques use mathematical models and algorithms to compute 3D tomography from 2D recordings on the scalp. In the case of epilepsy, EEG allows epileptic foci identification among propagation sites when it is recorded with a sufficient number of electrodes (> 100) and when realistic head models are used. The functional imaging techniques from nuclear medicine (PET and SPECT) have become very useful in neuroscience to explore cerebral changes associated with neuronal pathologies as well as cognitive and sensory tasks. Many efforts have been made to develop new cameras and models to increase the range of research and clinical applications. Co-registration of structural and functional images allows us to add functional information to a structural deficit, or conversely to better interpret functional images such as PET, SPECT and EEG in terms of specific anatomy. In the case of SPECT and fMRI, substraction between ictal and interictal exams points out areas involved in epileptic processes.

Standardized uptake value of 2-[(18)F] fluoro-2-deoxy-D-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy.

PURPOSE: In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy. PATIENTS AND METHODS: We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy. RESULTS: In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P =.01) and DFS (42% v 79%, P =.005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV. CONCLUSION: FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.

Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas.

5-Iodo-2'-deoxyuridine (IdUrd), a thymidine (TdR) analogue, can be radiolabelled with iodine-125, an Auger radiation emitter, to provoke double-strand breaks once incorporated into DNA of cancer cells. We have previously shown that co-incubation of [125I]IdUrd with unlabelled IdUrd provided an additive cytotoxicity in two human glioblastoma cell lines. This observation was unexpectedly correlated with an increase in the rate of DNA incorporation of [125I]IdUrd. Here, we further evaluated the effects of unlabelled IdUrd on the uptake of [125I]IdUrd in vitro and in vivo in mice xenografted with three human glioblastoma lines. The results showed that, in these three glioblastoma lines, unlabelled IdUrd increased the rate of uptake of [125I]IdUrd in vitro by 2- to 4.4-fold and in vivo by 1.5- to 2.8-fold. The rate of uptake of [125I]IdUrd in normal rapidly dividing tissues was also increased by 1.3- to 2.8-fold. TdR completely blocked [125I]IdUrd uptake in tumours and tissues. Analogues of IdUrd, such as deoxyuridine and 5-iodo-1,3-dimethyuracil, did not reproduce the effect of IdUrd on the uptake of [125I]IdUrd, suggesting that it is not related to protection against [125I]IdUrd degradation. It is concluded that combined administration of unlabelled IdUrd may improve the use of radiolabelled IdUrd for cancer diagnosis or therapy.