Functional imaging studies of cognition using 99mTc-HMPAO SPECT: empirical validation using the n-back working memory paradigm

{Purpose} Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of the study was to assess the feasibility of a split-dose activation protocol with 99mTc-HMPAO using low irradiation dose. {Materials and methods} A two-scans protocol was applied to 12 healthy young volunteers using 270 MBq of 99mTc-HMPAO per scan, with each image associated to a particular experimental condition of the verbal {n}-back working memory task (0-back, 2-back). Subtraction method was used to identify regional brain activity related to the task. {Results} Voxel-wise statistical analysis showed left lateralized activity associated with the 2-back task, compared to the 0-back task. Activated regions, mainly prefrontal and parietal, were similar to those observed in previous fMRI and 15O-PET studies. {Conclusion} The results support the use of 99mTc-HMPAO SPECT for the investigation of brain-cognition relations and demonstrate the feasibility of optimal quality images despite low radiopharmaceutical doses. The findings also acknowledge the use of HMPAO as a radioligand to capture neuro-energetic modulations linked to cognitive activity. They encourage extending the application of the described activation protocol to clinical populations

Surgical management of pulmonary inflammatory pseudotumors: A single center experience

<p>Abstract</p> <p>Background</p> <p>The pulmonary inflammatory pseudotumor (PIP) is a rare disease. It is still debated whether it represents an inflammatory lesion characterized by uncontrolled cell growth or a true neoplasm. PIP is characterized by a cellular polymorphism.</p> <p>Methods</p> <p>We retrospectively analyzed 8 patients with PIP treated by surgery between 2001 and 2009. Preoperative thoracic computed tomography (CT) scan was performed in all cases. All patients underwent preoperative bronchoscopy with washing and brushing and/or transbronchial biopsy and preoperative cytology examination</p> <p>Results</p> <p>There were 5 men and 3 women, aged between 38 and 69 years (mean of 58 years). 3 patients (37%) were asymptomatic. The others had symptoms characterized by chest pain, shortness of breath and persistent cough or hemoptysis. 5 patients had neutrophilic leucocytosis. CT scan demonstrated solitary nodules (maximum diameter <3 cm) in 5 patients (62%) and lung masses (maximum diameter >3 cm) in 3 patients (37%). In 2 patients there were signs of pleural infiltration. Distant lesions were excluded in all cases. A preoperative histology examination failed to reach a definitive diagnosis in all patients. At surgery, we performed two lobectomies, one segmentectomy and five wedge resections, these being performed with videothoracoscopy (VATS), except for one patient where open surgery was used. Complete tumor resection was obtained in all patients. According to the Matsubara classification, there were 2 cases of organizing pneumonia, 5 cases of fibrous histiocytoma and one case of lymphoplasmacytoma. All patients were discharged alive from hospital between 4 and 7 days after surgery. At follow-up CT scan performed annually (range 11 to 112 months) (mean 58 months), there were no residual lesions, neither local nor distant recurrences.</p> <p>Conclusions</p> <p>PIP is a rare disease. Many synonyms have been used for this disease, usually in relation to the most represented cell type. The true incidence is unclear. Preoperative diagnosis is difficult to reach, despite performing a bronchoscopy or a transparietal needle aspiration. Different classifications have been proposed for PIP. Either medical, radiation or surgical therapy has been used for PIP. Whenever possible, surgery should be considered the standard treatment. Complete surgical resection is advocated to prevent recurrence.</p

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博士（学術）神戸大

Medical imaging in presurgical investigation of epilepsy and new perspectives

In the presurgical epilepsy group, part of the project Vaud-Genève, medical imaging plays an important role in identifying the epileptic focus by means of volumetric measurement of the hippocampi and fusion of high resolution MRI with nuclear imaging PET and SPECT. New approaches are now developing such as functional MR triggered with EEG and MR spectroscopy to restrict the indications of invasive surgical exploration needed when no clear locus is demonstrated by standard medical imaging

Le pic de masse osseuse: realites et incertitudes. [Peak bone mass: facts and uncertainties]

Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk in adulthood. The techniques of single or dual energy absorptiometry measure the so-called "areal" or "surface" bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness, as there is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. At the beginning of the 3rd decade, there is a large variability in the normal values of areal BMD in axial and appendicular skeleton. This large variance, which is observed at sites particularly susceptible to osteoporotic fractures in adulthood, such as lumbar spine and femoral neck, is barely reduced after correction for statural height, and does not appear to substantially increase during adult life. It is generally accepted that peak bone mass at any skeletal site is attained in both sexes during the mid-thirties. However, recent studies indicate that in healthy caucasian females, bone mass accumulation can virtually be completed before the end of the second decade, for both lumbar spine and femoral neck. Several variables are supposed to influence bone mass accumulation during growth: heredity, sex, diet components, endocrine factors, mechanical forces, and exposure to risk factors.(ABSTRACT TRUNCATED AT 250 WORDS

Peak bone mass

Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk. Measurement of bone mass development. The bone mass of a given part of the skeleton is directly dependent upon both its volume or size and the density of the mineralized tissue contained within the periosteal envelope. The techniques of single-1 and dural-energy photon or X-ray absorptiometry measure the so-called 'areal' or 'surface' bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. Bone mass gain during puberty. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness. Puberty affects bone size much more than the volumetric mineral density. There is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. During puberty, the accumulation rate in areal BMD at both the lumbar spine and femoral neck levels increases to four- to sixfold over a 3- and 4-year period in females and males, respectively. Change in bone mass accumulation rate is less marked in long bone diaphyses. There is an asynchrony between the gain in statural height and bone mass growth. This phenomenon may be responsible for the occurrence of a transient period of a relative increase in bone fragility that may account for the pattern of fracture incidence during adolescence.(ABSTRACT TRUNCATED AT 250 WORDS

Functional neuroanatomical correlates of hysterical sensorimotor loss

Hysterical conversion disorders refer to functional neurological deficits such as paralysis, anaesthesia or blindness not caused by organic damage but associated with emotional 'spsychogenic' disturbances. Symptoms are not intentionally feigned by the patients whose handicap often outweighs possible short-term gains. Neural concomitants of their altered experience of sensation and volition are still not known. We assessed brain functional activation in seven patients with unilateral hysterical sensorimotor loss during passive vibratory stimulation of both hands, when their deficit was present and 2-4 months later when they had recovered. Single photon emission computerized tomography using 99mTc-ECD revealed a consistent decrease of regional cerebral blood flow in the thalamus and basal ganglia contralateral to the deficit. Independent parametric mapping and principal component statistical analyses converged to show that such subcortical asymmetries were present in each subject. Importantly, contralateral basal ganglia and thalamic hypoactivation resolved after recovery. Furthermore, lower activation in contralateral caudate during hysterical conversion symptoms predicted poor recovery at follow-up. These results suggest that hysterical conversion deficits may entail a functional disorder in striatothalamocortical circuits controlling sensorimotor function and voluntary motor behaviour. Basal ganglia, especially the caudate nucleus, might be particularly well situated to modulate motor processes based on emotional and situational cues from the limbic system. Remarkably, the same subcortical premotor circuits are also involved in unilateral motor neglect after organic neurological damage, where voluntary limb use may fail despite a lack of true paralysis and intact primary sensorimotor pathways. These findings provide novel constraints for a modern psychobiological theory of hysteri

Timing effects of combined radioimmunotherapy and radiotherapy on a human solid tumor in nude mice.

Timing effects of radioimmunotherapy (RIT) combined with external-beam radiotherapy (RT) were assessed in human colon carcinoma xenografts. Initially, dose effects of fractionated RT and RIT were evaluated separately. Then, 30 Gy RT (10 fractions over 12 days) were combined with three weekly i.v. injections of 200 microCi of 131I-labeled anti-carcinoembryonic antigen monoclonal antibodies in four different treatment schedules. RIT was given either prior to, concurrently, immediately after, or 2 weeks after RT administration. The longest regrowth delay (RD) of 105 days was observed in mice treated by concurrent administration of RT and RIT, whereas the RDs of RT and RIT alone were 34 and 20 days, respectively. The three sequential combination treatments produced significantly shorter RDs ranging from 62 to 70 days. The tumor response represented by the minimal volume (MV) also showed that concurrent administration of RT and RIT gave the best result, with a mean MV of 4.5% as compared to MVs from 26 to 53% for the three sequential treatments. The results were confirmed in a second experiment, in which a RT of 40 Gy was combined with an identical RIT as above (three injections of 200 microCi of 131I-labeled monoclonal antibodies). At comparable toxicity levels, the maximum tolerated RT or RIT alone gave shorter RDs and less tumor shrinkage compared to simultaneous RT+ RIT. These results may be useful for designing clinical protocols of combined RIT and RT

Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine.

Use of radiolabeled nucleotides for tumor imaging is hampered by rapid in vivo degradation and low DNA-incorporation rates. We evaluated whether blocking of thymidine (dThd) synthesis by 5-fluoro-2'-deoxyuridine (FdUrd) could improve scintigraphy with radio-dThd analogues, such as 5-iodo-2'-deoxyuridine (IdUrd). We first show in vitro that coincubation with FdUrd substantially increased incorporation of [125I]IdUrd and [3H]dThd in the three tested human glioblastoma lines. Flow cytometry analysis showed that a short coincubation with FdUrd (1 h) produces a signal increase per labeled cell. We then measured biodistribution 24 h after i.v. injection of [125I]IdUrd in nude mice s.c. xenografted with the three glioblastoma lines. Compared with animals given [125I]IdUrd alone, i.v. preadministration for 1 h of 10 mg/kg FdUrd increased the uptake of [125I]IdUrd in the three tumors 4.8-6.8-fold. Compatible with previous reports, there were no side effects in mice observed for 2 months after receiving such a treatment. The tumor uptake of [125I]IdUrd was increased &lt; or =13.6-fold when FdUrd preadministration was stepwise reduced to 1.1 mg/kg. Uptake increases remained lower (between 1.7- and 5.8-fold) in normal proliferating tissues (i.e., bone marrow, spleen, and intestine) and negligible in quiescent tissues. DNA extraction showed that 72-80% of radioactivity in tumor and intestine was bound to DNA. Scintigraphy of xenografted mice was performed at different times after i.v. injection of 3.7 MBq [125I]IdUrd. Tumor detection was significantly improved after FdUrd preadministration while still equivocal after 24 h in mice given [125I]IdUrd alone. Furthermore, background activity could be greatly reduced by p.o. administration of KClO4 in addition to potassium iodide. We conclude that FdUrd preadministration may improve positron or single photon emission tomography with cell division tracers, such as radio-IdUrd and possibly other dThd analogues

La radiothérapie systémique isotopique

La radiothérapie systémique à ['131] dans les cancers différentiés de la thyroïde offre une option thérapeutique spécifique et efficace. La thérapie isotopique palliative de métastases osseuses des cancers de la prostate et du sein a une action antalgique reconnue. Concernant les nouveaux développements, la radioimmunothérapie des lymphomes B non hodgkiniens de bas grade par des anticorps anti-CD20 marqués à a prouvé son efficacité. Nous serons en mesure de proposer cette thérapie prochainement à Genève et à Lausanne dans le cadre d'une étude phase III. Dans la radioimmunothérapie des tumeurs solides, la démonstration d'efficacité reste un défi important. La thérapie des cancers neuroendocriniens par un analogue de la somatostatine radiomarqué, a donné de premiers résultats intéressants dans une étude initiée à Bâle