Associations of Stages of Objective Memory Impairment with Cerebrospinal Fluid and Neuroimaging Biomarkers of Alzheimer's Disease.

OBJECTIVE: To investigate cerebrospinal fluid (CSF) and neuroimaging correlates of Stages of Objective Memory Impairment (SOMI) based on Free and Cued Selective Reminding Test (FCSRT) performance, and to evaluate the effect of APOE ε4 status on this relationship. METHODS: Data from 586 cognitively unimpaired individuals who had FCSRT, CSF, and volumetric magnetic resonance imaging (MRI) measures available was used. We compared CSF measures of ß-amyloid (Aß42/Aß40 ratio), phosphorylated tau (p-Tau181), total tau (t-Tau), hippocampal volume, and PIB-PET mean cortical binding potential with partial volume correction (MCBP) among SOMI groups in the whole sample and in subsamples stratified by APOE ε4 status. RESULTS: Participants had a mean age of 67.4 (SD=9.1) years, had 16.1 (SD=2.6) years of education, 57.0% were female, and 33.8% were APOE ε4 positive. In the entire sample, there was no significant difference between SOMI stages in Aß42/Aß40 ratio, p-Tau181, t-Tau, or PIB-PET MCBP when adjusted for age, sex, and education. However, higher SOMI stages had smaller hippocampal volume (F=3.29, p=0.020). In the stratified sample based on APOE ε4 status, in APOE ε4 positive individuals, higher SOMI stages had higher p-Tau181 (F=2.94, p=0.034) higher t-Tau (F=3.41, p=0.019), and smaller hippocampal volume (F=5.78, p<0.001). There were no significant differences in CSF or imaging biomarkers between SOMI groups in the APOE ε4 negative subsample. CONCLUSION: Cognitively normal older individuals with higher SOMI stages have higher in-vivo tau and neurodegenerative pathology only in APOE ε4 carriers. These original results indicate the potential usefulness of the SOMI staging system in assessing of tau and neurodegenerative pathology.

Neutron dose in and out of 18MV photon fields.

In radiation therapy, neutron contamination is an undesirable side effect of using high energy photons to treat patients. Neutron contamination requires adjustments to the shielding requirements of the linear accelerator vault and contributes to the risk of secondary malignancies in patients by delivering dose outside of the primary treatment field. Using MCNPX, an established Monte Carlo code, manufacturer blueprints, and the most up to date ICRP neutron dose conversion factors, the neutron spectra, neutron/photon dose ratio, and the neutron capture gamma ray dose were calculated at different depths and off axis distances in a tissue equivalent phantom. Results demonstrated that the neutron spectra and dose are dependent on field size, depth in the phantom, and off-axis distance. Simulations showed that because of the low neutron absorption cross section of the linear accelerator head materials, the contribution to overall patient dose from neutrons can be up to 1000 times the photon dose out of the treatment field and is also dependent on field size and depth. Beyond 45cm off-axis, the dependence of the neutron dose on field size is minimal. Neutron capture gamma ray dose is also field size dependent and is at a maximum at a depth of about 7cm. It is important to remember that when treating with high energy photons, the dose from contamination neutrons must be considered as it is much greater than the photon dose.

The effect of energy spectrum change on DNA damage in and out of field in 10-MV clinical photon beams.

The aim of this study was to quantify the DNA damage induced in a clinical megavoltage photon beam at various depths in and out of the field. MCNPX was used to simulate 10 × 10 and 20 × 20 cm(2) 10-MV photon beams from a clinical linear accelerator. Photon and electron spectra were collected in a water phantom at depths of 2.5, 12.5 and 22.5 cm on the central axis and at off-axis points out to 10 cm. These spectra were used as an input to a validated microdosimetric Monte Carlo code, MCDS, to calculate the RBE of induced DSB in DNA at points in and out of the primary radiation field at three depths. There was an observable difference in the energy spectra for photons and electrons for points in the primary radiation field and those points out of field. In the out-of-field region, the mean energy for the photon and electron spectra decreased by a factor of about six and three from the in-field mean energy, respectively. Despite the differences in spectra and mean energy, the change in RBE was <1 % from the in-field region to the out-of-field region at any depth. There was no significant change in RBE regardless of the location in the phantom. Although there are differences in both the photon and electron spectra, these changes do not correlate with a change in RBE in a clinical MV photon beam as the electron spectra are dominated by electrons with energies >20 keV.

Aneurysmal bone cyst: its pathogenesis based on angiographic, immunohistochemical and electron microscopic studies.

Based on angiographic, immunohistochemical as well as electron microscopic findings, authors outline a hypothesis for the etiopathogenesis of aneurysmal bone cysts. No changes were found at the arterial site in 16 studied aneurysmal bone cysts, with no signs of an arteriovenous shunt. In certain cases, however, dilated and tortous efferent veins became visible in the late venous phase. Due to the impedance of venous flow, the intracystic pressure increases and the small veins become dilated causing formation of aneurysmal slits. This is supported by the immunohistochemical finding that S-actin shows concentric arrangement around the aneurysmal cavities. Endothelial lining and basal membrane remnants were detectable in places, though the aneurysmal slits were devoid of continuous endothelial lining and basal membrane. We suggested that the aneurysmal bone cyst corresponds to a hemodynamic disturbance and is due to primary or secondary venous malformation of the bones.