Semiautomatic method to identify the best phase for gated RT in lung region by 4D-PET/CT acquisitions.

PURPOSE: Delineating tumor motion by four-dimensional positron emission tomography/computed tomography (4D-PET/CT) is a crucial step for gated radiotherapy (RT). This article quantitatively evaluates semiautomatic algorithms for tumor shift estimation in the lung region due to patient respiration by 4D-PET/CT, in order to support the selection of the best phases for gated RT, by considering the most stable phases of the breathing cycle. METHODS: Three mobile spheres and ten selected lesions were included in this study. 4D-PET/CT data were reconstructed and classified into six/ten phases. The semiautomatic algorithms required the generation of single sets of images representative of the full target motion, used as masks for segmenting the phases. For 4D-CT, a pre-established HU range was used, whereas three thresholds (100%, 80%, and 40%) were evaluated for 4D-PET. By using these segmentations, the authors estimated the lesion motion from the shifting centroids, and the phases with the least motion were also deduced including the phases with a curve slope less than 2 mm/ delta phase. The proposed algorithms were validated by comparing the results to those generated entirely by manual contouring. RESULTS: In the phantom study, the mean difference between the manual contour and the semiautomatic technique was 0.1 +/- 0.1 mm for 4D-CT and 0.2 +/- 0.1 mm for the 4D-PET based on 40% threshold. In the patients' series, the mean difference was 0.9 +/- 0.6 mm for 4D-CT and 0.8 +/- 0.2 mm for the 4D-PET based on 40% threshold. CONCLUSIONS: Estimation of lesion motion by the proposed semiautomatic algorithm can be used to evaluate tumor motion due to breathing.

Use of PET and PET/CT for radiation therapy planning: IAEA expert report 2006-2007.

Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants' meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, (18)F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.

Training-induced brain remapping in chronic aphasia: a pilot study.

BACKGROUND: The neural correlates of training-induced improvements of cognitive functions after brain damage remain still scarcely understood. In the specific case of aphasia, although several investigations have addressed the issue of the neural substrates of functional recovery, only a few studies have attempted to assess the impact of language training on the damaged brain. AIMS: The main goal of this study was to examine the neurobiological correlates of improved picture-naming performance in 2 aphasic patients who received intensive and specific training for a chronic and severe phonological anomia. METHODS: In both participants, picture-naming performance was assessed before and after phonological cueing training. Training-induced changes in patients' performance were correlated to brain activity patterns as revealed by pre- and post-training event-related functional magnetic resonance imaging scanning. RESULTS: Training-induced improvement was observed concurrently with changes in the brain activation patterns. Better performance was observed in the patient with the smaller lesion, partially sparing Broca's area, who showed a left perilesional reactivation. Conversely, the patient with complete destruction of Broca's area showed a posttraining activation in the right mirror frontal region. CONCLUSIONS: The results show that, even in the chronic stage, phonological strategies may improve impaired naming and induce cerebral reorganization.

Neuropsychological deficits and neural dysfunction in familial dyslexia.

We report the neuropsychological profile and the pattern of brain activity during reading tasks in a sample of familial dyslexics. We studied our subjects with an in-depth neuropsychological assessment and with functional neuroimaging (fMRI) during word and pseudoword reading and false font string observations (baseline condition). The neuropsychological assessment revealed that familial dyslexia, in both persistent and compensated forms, is often associated with deficits in verbal short-term memory, phonological awareness and automatization abilities. The functional results showed a lack of activation in the posterior areas of the reading network. This study, together with the previously published VBM study (Brambati, S.M., Termine, C., Ruffino, M., Stella, G., Fazio, F., Cappa, S.F. and Perani, D., Regional reductions of gray matter volume in familial dyslexia, Neurology, 63 (2004) 742-5), provides a multiple modality evaluation of familial dyslexia. The neuropsychological assessment showed cognitive deficits associated with dyslexia that persist also in subjects with compensated reading deficit. Both the anatomical and the functional study point out a deficit in the posterior areas of the reading network.

Early use of artificial sensibility in hand transplantation.

Hands were transplanted from brain-dead donors for the treatment of two male unilateral amputees, aged 35 years and 32 years, involved in the Italian Hand Transplantation Programme. Each had lost his right dominant hand, in a farming accident and an explosion, respectively. In one case artificial sensibility was applied postoperatively using a Sensor Glove that transformed vibrotactile stimuli induced by touch, to stereophonic vibroacoustic stimuli perceived through earphones. The principle is based on the brain's capacity for multimodal plasticity, implying that deprivation of one sense (somatosensory) can be compensated for by another sense (auditory). Functional magnetic resonance images (fMRI) taken at regular intervals showed that cortical remodelling of the transplanted hand within the sensory-motor maps occurred early in the patient who used the artificial sensibility regimen compared with the one who did not. We conclude that postoperative use of a device using hearing as a substitution for sensation in hand transplantation may have considerable potential value for speeding up cortical integration of a transplanted hand.

The impact of semantic reference on word class: an fMRI study of action and object naming.

There is a considerable body of neuropsychological and neuroimaging evidence supporting the distinction between the brain correlates of noun and verb processing. It is however still not clear whether the observed differences are imputable to grammatical or semantic factors. Beyond the basic difference that verbs typically refer to actions and nouns typically refer to objects, other semantic distinctions might play a role as organizing principles within and across word classes. One possible candidate is the notion of manipulation and manipulability, which may modulate the word class dissociation. We used functional magnetic resonance imaging (fMRI) to study the impact of semantic reference and word class on brain activity during a picture naming task. Participants named pictures of objects and actions that did or did not involve manipulation. We observed extensive differences in activation associated with the manipulation dimension. In the case of manipulable items, for both nouns and verbs, there were significant activations within a fronto-parietal system subserving hand action representation. However, we found no significant effect of word class when all verbs were compared to all nouns. These results highlight the impact of the biologically crucial sensorimotor dimension of manipulability on the pattern of brain activity associated to picture naming.

The effect of social content on deductive reasoning: an fMRI study.

Psychological studies of deductive reasoning have shown that subjects' performance is affected significantly by the content of the presented stimuli. Specifically, subjects find it easier to reason about contexts and situations with a social content. In the present study, the effect of content on brain activation was investigated with functional magnetic resonance imaging (fMRI) while subjects were solving two versions of the Wason selection task, which previous behavioral studies have shown to elicit a significant content effect. One version described an arbitrary relation between two actions (Descriptive: "If someone does ..., then he does ..."), whereas the other described an exchange of goods between two persons (Social-Exchange: "If you give me ..., then I give you ..."). Random-effect statistical analyses showed that compared to baseline, both tasks activated frontal medial cortex and left dorsolateral frontal and parietal regions, confirming the major role of the left hemisphere in deductive reasoning. In addition, although the two reasoning conditions were identical in logical form, the social-exchange task was also associated with right frontal and parietal activations, mirroring the left-sided activations common to both reasoning tasks. These results suggest that the recruitment of the right hemisphere is dependent on the content of the stimuli presented.

Listening to action-related sentences activates fronto-parietal motor circuits.

Observing actions made by others activates the cortical circuits responsible for the planning and execution of those same actions. This observation-execution matching system (mirror-neuron system) is thought to play an important role in the understanding of actions made by others. In an fMRI experiment, we tested whether this system also becomes active during the processing of action-related sentences. Participants listened to sentences describing actions performed with the mouth, the hand, or the leg. Abstract sentences of comparable syntactic structure were used as control stimuli. The results showed that listening to action-related sentences activates a left fronto-parieto-temporal network that includes the pars opercularis of the inferior frontal gyrus (Broca's area), those sectors of the premotor cortex where the actions described are motorically coded, as well as the inferior parietal lobule, the intraparietal sulcus, and the posterior middle temporal gyrus. These data provide the first direct evidence that listening to sentences that describe actions engages the visuomotor circuits which subserve action execution and observation.

Cross-sectional assessment of the effect of kidney and kidney-pancreas transplantation on resting left ventricular energy metabolism in type 1 diabetic-uremic patients: a phosphorous-31 magnetic resonance spectroscopy study.

OBJECTIVES: To test whether left ventricular (LV) dysfunction affecting type 1 diabetic-uremic patients was associated with abnormal heart high-energy phosphates (HEPs) and to ascertain whether these alterations were also present in recipients of kidney or kidney-pancreas transplantation. BACKGROUND: Heart failure is the major determinant of mortality in patients with diabetic uremia. Both uremia and diabetes induce alterations of cardiac HEPs metabolism. METHODS: Magnetic resonance imaging and phosphorous magnetic resonance spectroscopy of the LV were performed in the resting state by means of a 1.5-T clinical scanner. Eleven diabetic-uremic patients, 5 nondiabetic patients with uremia, 11 diabetic recipients of kidney transplantation, and 16 diabetic recipients of combined kidney-pancreas transplantation were studied in a cross-sectional fashion. Eleven nondiabetic recipients of kidney-only transplant and 13 healthy subjects served as control groups. RESULTS: Uremic patients had higher LV mass, diastolic dysfunction, and lower phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio in comparison with recipients of kidney-pancreas or nondiabetic recipients of kidney transplant. In diabetic recipients of kidney transplant the PCr/ATP ratio was higher than in uremic patients but was lower than in the controls. Recipients of combined kidney-pancreas transplant had a higher ratio than uremic patients but no difference was found in comparison with controls. CONCLUSIONS: Altered resting myocardial HEPs metabolism may contribute to LV dysfunction in diabetic-uremic patients. In diabetic recipients of kidney transplantation, a certain degree of LV metabolic and functional impairment was found. In combined kidney-pancreas recipients the resting LV metabolism and function were not different than in controls.

Normal insulin sensitivity and IMCL content in overweight humans are associated with higher fasting lipid oxidation.

Intramyocellular lipid (IMCL) storage is considered a local marker of whole body insulin resistance; because increments of body weight are supposed to impair insulin sensitivity, this study was designed to assess IMCL content, lipid oxidation, and insulin action in individuals with a moderate increment of body fat mass and no family history of diabetes. We studied 14 young, nonobese women with body fat <30% (n = 7) or >30% (n = 7) and 14 young, nonobese men with body fat <25% (n = 7) or >25% (n = 7) by means of the euglycemic-insulin clamp to assess whole body glucose metabolism, with indirect calorimetry to assess lipid oxidation, by localized (1)H NMR spectroscopy of the calf muscles to assess IMCL content, and with dual-energy X-ray absorptiometry to assess body composition. Subjects with higher body fat had normal insulin-stimulated glucose disposal (P = 0.80), IMCL content in both soleus (P = 0.22) and tibialis anterior (P = 0.75) muscles, and plasma free fatty acid levels (P = 0.075) compared with leaner subjects in association with increased lipid oxidation (P < 0.05), resting energy expenditure (P = 0.046), resting oxygen consumption (P = 0.049), and plasma leptin levels (P < 0.01) in the postabsorptive condition. In conclusion, in overweight subjects, preservation of insulin sensitivity was combined with increased lipid oxidation and maintenance of normal IMCL content, suggesting that abnormalities of these factors may mutually determine the development of insulin resistance associated with weight gain.

Performance evaluation of the new whole-body PET/CT scanner: Discovery ST.

Characterisation of the physical performance of the new integrated PET/CT system Discovery ST (GE Medical Systems) has been performed following the NEMA NU 2-1994 (N-94) and the NEMA NU 2-2001 (N-01) standards in both 2D and 3D acquisition configuration. The Discovery ST combines a four or eight multi-slice helical CT scanner with a PET tomograph which consists of 10,080 BGO crystals arranged in 24 rings. The crystal dimensions are 6.3 x 6.3 x 30 mm(3) and they are organised in blocks of 6 x 6 crystals, coupled to a single photomultiplier tube with four anodes. The 24 rings of the PET system allow 47 images to be obtained, spaced by 3.27 mm, and covering an axial field of view of 157 mm. The low- and high-energy thresholds are set to 375 and 650 keV, respectively. The coincidence time window is set to 11.7 ns. Using the NEMA N-94 standard, the main results were: (1) the average (radial and tangential) transverse spatial resolution (FWHM) at 1, 10 and 20 cm off axis was 6.28 mm, 7.09 mm and 7.45 mm in 2D, and 6.68 mm, 7.72 mm and 8.13 mm in 3D; (2) the sensitivity for true events was 8,567 cps/kBq/cc in 2D and 36,649 cps/kBq/cc in 3D; (3) the scatter fraction was 15% in 2D and 30% in 3D; (4) the peak true events rate, the true events rate at 50% of the system dead-time and the true events rate when equal to the random events rate were 750 kcps at 189.81 kBq/cc, 744 kcps at 186.48 kBq/cc and 686 kcps at 150.59 kBq/cc, respectively, in 2D, and 922 kcps at 44.03 kBq/cc, 834 kcps at 53.28 kBq/cc and 921 kcps at 44.03 kBq/cc in 3D; (5) the noise equivalent count (NEC) peak rate was 270 kcps at 34.38 kBq/cc in 3D, with random coincidences estimated by delayed events. Using the NEMA N-01 standards the main results were: (1) the average transverse and axial spatial resolution (FWHM) at 1 cm and 10 cm off axis was 6.28 (4.56) mm and 6.88 (6.11) mm in 2D, and 6.29 (5.68) mm and 6.82 (6.05) mm in 3D; (2) the average sensitivity for the two radial positions (r=0 cm and r=10 cm) was 1.93 cps/kBq in 2D and 9.12 cps/kBq in 3D; (3) the scatter fraction was 19% in 2D and 45% in 3D; (4) the NEC peak rate was 54 kcps at 46.99 kBq/cc in 2D and 45.5 kcps at 10.84 kBq/cc in 3D, when random coincidences were estimated by using k=2 in the NEC formula, while the NEC peak rate was 81 kcps at 64.43 kBq/cc and 66 kcps at 14.86 kBq/cc in 2D and 3D, respectively, when random coincidences were estimated by using k=1 in the NEC formula. The new integrated PET-CT system Discovery ST has good overall performances in both 2D and 3D, with in particular a high sensitivity and a very good 3D NEC response.

Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes.

Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2H2]glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 +/- 0.6 and 3.2 +/- 0.8 ml x kg(-1) min(-1)) similar to OFF (5.3 +/- 0.4 ml x kg(-1) x min(-1)) compared with NOR (8.5 +/- 0.5 ml x kg(-1) min(-1), P < 0.001). Soleus IMCL content was increased in T1DM (112 +/- 15 AU), T2DM (108 +/- 10 AU) and OFF (82 +/- 13 AU) compared with NOR (52 +/- 7 AU, P < 0.05) and the result was inversely proportional to the MCR (R2 = 0.27, P < 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R2 = 0.57, P < 0.001). Fasting plasma adiponectin was reduced in T2DM (7 +/- 1 microg/ml, P = 0.01) and OFF (11 +/- 1 microg/ml, P = 0.03) but not in T1DM (25 +/- 6 microg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 +/- 2 microg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.