The authors developed and applied two new linearized reference tissue models for parametric images of binding potential ( BP) and relative delivery ( R1) for [11C]DASB positron emission tomography imaging of serotonin transporters in human brain. The original multilinear reference tissue model (MRTMO) was modified (MRTM) and used to estimate a clearance rate ( k′2) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM2) by fixing k′2. The resulting BP and R1 estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [11C]DASB data. MRTM gave k′2 estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTMO from 12–70% to 1–4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of two or three over MRTM or SRTM. MRTM2, SRTM2, and 1TKA had R1 bias <0.3% and variability at least a factor of two lower than MRTM or SRTM. MRTM2 allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM2 should be a useful method for human [11C]DASB positron emission tomography studies.

Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R). D2R is expressed most highly in the striatum, but most of the recent positron emission tomography (PET) studies have failed to show any change in D2R densities in the striatum of schizophrenics, raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex, has been implicated in the control of working memory, and working memory dysfunction is a prominent feature of schizophrenia. We have therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of the negative symptoms (for instance, emotional withdrawal) and to poor performance in the Wisconsin Card Sorting Test. We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.

We provide the first evidence for the capability of a high-resolution positron emission tomographic (PET) imaging system in quantitatively mapping amyloid accumulation in living amyloid precursor protein transgenic (Tg) mice. After the intravenous administration of N-[ Our results support the usefulness of the small animal-dedicated PET system in conjunction with high-specific radioactivity probes and appropriate Tg models not only for clarifying the mechanistic properties of amyloidogenesis in mouse models but also for preclinical tests of emerging diagnostic and therapeutic approaches to AD.

A nationwide statistical survey of 4098 dialysis facilities was conducted at the end of 2007, and 4052 facilities (98.88%) participated. The number of patients undergoing dialysis at the end of 2007 was determined to be 275 242, an increase of 10 769 patients (4.1%) compared with that at the end of 2006.The number of dialysis patients per million at the end of 2007 was 2154. The crude death rate of dialysis patients at the end of 2007 from the end of 2006 was 9.4%. The mean age of new patients begun on dialysis was 66.8 years and the mean age of the entire dialysis patient population was 64.9 years. For the primary diseases of new patients begun on dialysis, the percentages of patients with diabetic nephropathy and chronic glomerulonephritis were 43.4% and 23.8%, respectively. The percentages of facilities that achieved the control standard of endotoxin concentration in the dialysate solution of<0.05 EU/mL and those that achieved a bacterial count of <100 cfu/mL in the dialysate solution, as specified by the Japanese Society for Dialysis Therapy, were 93.6% and 97.4%, respectively. The percentage of patients positive for the hepatitis C virus antibody among the entire dialysis population significantly decreased from 15.95% at the end of 1999 to 9.83% at the end of 2007. The mean hemoglobin concentration in all the dialysis patients at the end of 2007 was 10.27 (+/-1.32, SD) g/dL, which has scarcely changed over the last three years. The numbers of male and female patients with a history of hip fracture were 142.9 and 339.0 per 10 000 dialysis patients, respectively, showing an extremely high prevalence among female patients. A history of hip fracture correlates with a low body mass index, serum albumin concentration, and a history of diabetes. The serum creatinine level of patients upon introduction to dialysis was 8.34 (+/-3.55) mg/dL, and the estimated glomerular filtration rate was 5.43 (+/-3.43) mL/min/1.73 m(2) for the patients who were newly begun on dialysis in 2007.

We demonstrate the significance of peripheral benzodiazepine receptor (PBR) imaging in living mouse models of Alzheimer's disease (AD) as biomarkers and functional signatures of glial activation. By radiochemically and immunohistochemically analyzing murine models of the two pathological hallmarks of AD, we found that AD-like A␤ deposition is concurrent with astrocyte-dominant PBR expression, in striking contrast with nonastroglial PBR upregulation in accumulations of AD-like phosphorylated tau. Because tauinduced massive neuronal loss was distinct from the marginal neurodegeneration associated with A␤ plaques in these models, cellular localization of PBR reflected deleterious and beneficial glial reactions to tau versus A␤ pathologies, respectively. This notion was subsequently examined in models of various non-AD neuropathologies, revealing the following reactive glial dynamics underlying differential PBR upregulation: (1) PBR(Ϫ) astrogliosis uncoupled with microgliosis or coupled with PBR(ϩ) microgliosis associated with irreversible neuronal insults; and (2) PBR(ϩ) astrogliosis coupled with PBR(Ϫ or Ϯ) microgliosis associated with minimal or reversible neuronal toxicity. Intracranial transplantation of microglia also indicated that nontoxic microglia drives astroglial PBR expression. Moreover, levels of glial cell line-derived neurotrophic factor (GDNF) in astrocytes were correlated with astroglial PBR, except for increased GDNF in PBR(-) astrocytes in the model of AD-like tau pathology, thereby suggesting that PBR upregulation in astrocytes is an indicator of neurotrophic support. Together, PBR expressions in astrocytes and microglia reflect beneficial and deleterious glial reactions, respectively, in diverse neurodegenerative disorders including AD, pointing to new applications of PBR imaging for monitoring the impact of gliosis on the pathogenesis and treatment of AD.