[(18)F]FMM PET imaging detects Aβ deposition in patients along the continuum from normal cognitive status to dementia of AD and discriminates AD patients from HC subjects, similar to [(11)C]PIB PET.

Focal cerebral ischemia was produced by occluding the left middle cerebral artery in 769 rats. Permeability of the blood-brain barrier to small or large molecules was evaluated qualitatively using Evans blue or sodium fluorescein and quantitatively using the transfer indexes of iodine-125-labeled bovine serum albumin or [ M C] sucrose. Water content was determined using wet and dry weights and sodium and potassium contents using flame photometry. Cortical tissue in the middle cerebral artery territory was sampled <14 days after occlusion. A significant increase in the albumin transfer index was first found 12 hours after occlusion, and the index remained approximately the same until water content peaked 3 days after occlusion. In contrast, the sucrose transfer index increased gradually, significantly correlated with increases in the water and sodium contents. Tissue staining by sodium fluorescein was more extensive than that by Evans blue. As edema fluid decreased gradually 4-10 days after occlusion, the albumin and sucrose transfer indexes increased markedly. These findings indicate that disruption of the blood-brain barrier to small molecules is accompanied by accumulation of edema fluid during the later stages of ischemia. Opening of the barrier to serum protein is probably related to the resolution of edema. (Stroke 1990;21:582-588)

Summary:The relationship of the osmotic pressure gra dient between blood and brain, and the development of ischemic brain edema was studied. Focal cerebral isch emia was produced by left middle cerebral artery occlu sion in rats. Brain osmolality was determined with a vapor pressure osmometer, brain water content by wet dry weight, and tissue sodium and potassium contents by flame photometry. Permeability of the BBB was tested by Evans blue. Measurements were made from the ischemic cortex within 14 days of occlusion. Brain osmolality in creased from 311 ± 2 to 329 ± 2 mOsm/kg by 6 h after occlusion. Serum osmolality did not change significantly. The osmotic gradient between blood and brain peaked at �26 mOsm/kg. Brain osmolality then decreased to 310 ± Water movement across the BBB into brain tissue presumably follows the Starling equation (Fenstermacher, 198 4;Rapoport, 1978 ). Many factors modify the edema process, but their contri butions to the formation and resolution of brain edema are poorly understood. These factors in clude cerebrovascular permeability, capillary hy draulic conductivity, hydrostatic and osmotic pres sure gradients, and tissue compliance and conduc tivity.Occlusion of a major end artery of the brain causes edema of varying degrees in and around the region supplied by that artery. Ischemic brain edema depends primarily on the duration and depth of ischemia (Astrup et aI., 198 1; Bell et aI., 198 5). In addition, hydraulic conductivity of capillary as well as hydrostatic and osmotic pressure gradients between blood and brain probably have an impor tant role in the ischemic edema process. We recently demonstrated that a hydrostatic pressure gradient across the capillary develops within minutes after the onset of ischemia and is the driving force for early accumulation of edema fluid (Hatashita and Hoff, 1986a,b). We also have shown that as the ischemic injury progresses, edema fluid accumulates in highly compliant brain parenchyma, then migrates through highly conduc tive tissue into the CSF spaces and is driven by a hydrostatic pressure gradient between the edema tous tissue and the CSF (Hatashita and Hoff, 198 8a). It remains unclear how osmotic pressure gradients across capillaries are associated with hy drostatic pressure gradients and hydraulic conduc tivity and how those gradients are influenced by the duration and degree of ischemia.The present experiment was designed to study whether an osmotic gradient across the capillary is associated with the development of ischemic brain edema and, if so, how the gradient is related to tissue electrolytes and permeability of the BBB. We attempted to clarify the relationship between brain tissue osmolality, brain edema, tissue sodium and potassium, and the integrity of the BBB in rats with focal cerebral ischemia.

Sixty patients with acute subdural hematoma were treated at Tokyo Metropolitan Hiroo Hospital between 1981 and 1989. The overall mortality was 55% and the functional recovery rate 30%. Thirteen (93%) of 14 patients with a Glasgow Coma Scale (GCS) score of 3 died, while all eight patients with a GCS score of 7 or more achieved functional recovery. The mortality of patients with GCS scores of 4-6 ranged from 45 to 67%. Patients with GCS scores of 4-6 over 65 years old had a mortality of 82%, compared to 50% mortality for those aged 19-40 years. The mortality for patients with GCS scores of 4-6 operated on within 4 hours of injury was 62% in contrast to 33% for those operated on from 4 to 10 hours. Patients with GCS scores of 4-6 who underwent craniotomy with evacuation of the hematoma achieved significantly better recovery than those treated by burr holes. Four patients with GCS scores of 4-6 died in spite of decompressive craniectomy or craniotomy with duroplasty. The mortality is only influenced by age and type of surgical intervention among patients with GCS scores of 4-6. Shorter time from injury to surgical evacuation does not affect mortality within 10 hours of injury.

The aim of this study is to identify mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) using amyloid imaging of beta amyloid (Aβ) deposition and FDG imaging of reflecting neuronal dysfunction as PET biomarkers. Sixty-eight MCI patients underwent cognitive testing, [11C]-PIB PET and [18F]-FDG PET at baseline and follow-up. Regions of interest were defined on co-registered MRI. PIB distribution volume ratio (DVR) was calculated using Logan graphical analysis, and the standardized uptake value ratio (SUVR) on the same regions was used as quantitative analysis for [18F]-FDG. Thirty (44.1%) of all 68 MCI patients converted to AD over 19.2±7.1 months. The annual rate of MCI conversion was 23.4%. A positive Aβ PET biomarker significantly identified MCI due to AD in individual MCI subjects with a sensitivity (SS) of 96.6% and specificity (SP) of 42.1%. The positive predictive value (PPV) was 56.8%. A positive Aβ biomarker in APOE ε4/4 carriers distinguished with a SS of 100%. In individual MCI subjects who had a prominent impairment in episodic memory and aged older than 75 years, an Aβ biomarker identified MCI due to AD with a greater SS of 100%, SP of 66.6% and PPV of 80%, compared to FDG biomarker alone or both PET biomarkers combined. In contrast, when assessed in precuneus, both Aβ and FDG biomarkers had the greatest level of certainty for MCI due to AD with a PPV of 87.8%. The Aβ PET biomarker primarily defines MCI due to AD in individual MCI subjects. Furthermore, combined FDG biomarker in a cortical region of precuneus provides an added diagnostic value in predicting AD over a short period.