Spect measurements of regional cerebral perfusion and carbondioxide reactivity: correlation with cerebral collaterals in internal carotid artery occlusive disease.

BACKGROUND: The aim of the present study was to assess the regional variation in cerebral perfusion, vasomotor reactivity (VMR) and the role of cerebral collaterals in patients with symptomatic internal carotid artery (ICA). METHODS: Seventeen functionally independent patients (60+/-9 years, mean+/-SD) with a unilateral symptomatic internal carotid artery occlusion and a <30% contralateral ICA stenosis were investigated. (99 m) Tc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) was performed to study cerebral blood flow in rest and during a CO(2) challenge in the cerebellum, temporal lobe, occipital lobe, basal ganglia, frontal lobe and parietal lobe. Time of flight and phase contrast MRA were used to study collateral flow via circle of Willis. RESULTS: In rest, cerebral perfusion on the side ipsilateral to the ICA occlusion was decreased compared with the contralateral side in the basal ganglia (p<0.05), frontal lobe (p<0.01) and parietal lobe (p<0.01). During a CO(2) challenge only the ipsilateral frontal lobe demonstrated a perfusion decrease compared with the contralateral frontal lobe (p<0.05). Furthermore, in patients without collateral flow via the anterior circle of Willis the perfusion of the ipsilateral frontal lobe was significantly decreased (p<0.01) during the CO(2) challenge and crossed cerebellar diaschisis with a decreased perfusion on the contralateral cerebellar hemisphere was detected (p<0.05). No cerebral blood flow (CBF) differences were found for present/absent collateral flow via the posterior communicating artery. CONCLUSION: Regional assessment of cerebral perfusion and VMR with SPECT demonstrated the heterogeneity of cerebral hemodynamics and the importance of collateral flow via the anterior circle of Willis.

Activated vitronectin as a target for anticancer therapy with human antibodies.

The formation of a provisional extracellular matrix represents an important step during tumor growth and angiogenesis. Proteins that participate in this process become activated and undergo conformational changes that expose biologically active cryptic sites. Activated matrix proteins express epitopes not found on their native counterparts. We hypothesized that these epitopes may have a restricted tissue distribution, rendering them suitable targets for therapeutic human monoclonal antibodies (huMabs). In this study, we exploited phage antibody display technology and subtractive phage selection to generate human monoclonal antibody fragments that discriminate between the activated and native conformation of the extracellular matrix protein vitronectin. One of the selected antibody fragments, scFv VN18, was used to construct a fully human IgG/kappa monoclonal antibody with an affinity of 9.3 nM. In immunohistochemical analysis, scFv and huMab VN18 recognized activated vitronectin in tumor tissues, whereas hardly any activated vitronectin was detectable in normal tissues. Iodine 123-radiolabeled huMabVN18 was shown to target to Rous sarcoma virus-induced tumors in chickens, an animal model in which the epitope for huMab VN18 is exposed during tumor development. Our results establish activated vitronectin as a potential target for tumor therapy in humans.

Monte Carlo-based down-scatter correction of SPECT attenuation maps.

Combined acquisition of transmission and emission data in single-photon emission computed tomography (SPECT) can be used for correction of non-uniform photon attenuation. However, down-scatter from a higher energy isotope (e.g. 99mTc) contaminates lower energy transmission data (e.g. 153Gd, 100 keV), resulting in underestimation of reconstructed attenuation coefficients. Window-based corrections are often not very accurate and increase noise in attenuation maps. We have developed a new correction scheme. It uses accurate scatter modelling to avoid noise amplification and does not require additional energy windows. The correction works as follows: Initially, an approximate attenuation map is reconstructed using down-scatter contaminated transmission data (step 1). An emission map is reconstructed based on the contaminated attenuation map (step 2). Based on this approximate 99mTc reconstruction and attenuation map, down-scatter in the 153Gd window is simulated using accelerated Monte Carlo simulation (step 3). This down-scatter estimate is used during reconstruction of a corrected attenuation map (step 4). Based on the corrected attenuation map, an improved 99mTc image is reconstructed (step 5). Steps 3-5 are repeated to incrementally improve the down-scatter estimate. The Monte Carlo simulator provides accurate down-scatter estimation with significantly less noise than down-scatter estimates acquired in an additional window. Errors in the reconstructed attenuation coefficients are reduced from ca. 40% to less than 5%. Furthermore, artefacts in 99mTc emission reconstructions are almost completely removed. These results are better than for window-based correction, both in simulation experiments and in physical phantom experiments. Monte Carlo down-scatter simulation in concert with statistical reconstruction provides accurate down-scatter correction of attenuation maps.