The Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of

Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers (QIBs) to measure changes in these features. Critical to the performance of a QIB in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method and metrics used to assess a QIB for clinical use. It is therefore, difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America (RSNA) and the Quantitative Imaging Biomarker Alliance (QIBA) with technical, radiological and statistical experts developed a set of technical performance analysis methods, metrics and study designs that provide terminology, metrics and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of QIB performance studies so that results from multiple studies can be compared, contrasted or combined.

The limited donor organ supply has led to several bridging techniques to sustain patients with acute and subacute liver failure. We report here the prospective, controlled trial of transplanted isolated fresh and cryopreserved human hepatocytes as a bridge to orthotopic liver transplantation. Five hepatocyte transplant recipients with grade IV encephalopathy and multisystem organ failure and four patients of equal illness severity due to liver failure were studied. Medical therapy resulted in a significant (P<0.05), but not normal, fall in blood ammonia, and a significant (P<0.02) resolving biochemical marker of liver injury that did not improve cardiovascular or cerebral stability; this lead to death within 3 days in all control patients. The five hepatocyte-treated patients maintained normal cerebral perfusion and cardiac stability, with withdrawal of medical support for 2 to 10 days before orthotopic liver transplantation. Biochemical evidence of liver injury improved significantly (P=0.004) and blood ammonia levels decreased significantly (P=0.0005) to normal levels in the hepatocyte-treated patients. Three of five patients who successfully bridged to whole liver allograft transplant are alive, home, and normal with more than 20 months of follow-up. No infections or embolic or pulmonary complications resulted from intra-arterial splenic hepatocyte infusion. Specific antiprotease production in a patients with genetically deficient alpha-1-antitrypsin disease, and immunohistochemical and electron microscopic evidence of splenic "hepatization" are presented as evidence of the viability of hepatocyte splenic seeding. In conclusion, splenic transplantation of differentiated adult hepatocytes can control hyper-ammonemia, correct genetic defects in liver function, and bridge life to orthotopic liver transplantation in human liver failure.

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