Quantification, anatomical standarisation and statistical analyses of human brain perfusion- and receptor data using Emission Tomography with applications in neurology and psychiatry

Diss. doct. medische wetenschappe

Non-invasive methods for absolute cerebral blood flow measurement using Tc-99m-ECD: a study in healthy volunteers

Radionuclide angiography with technetium-99m ethyl cysteinate dimer (ECD) allows non-invasive estimation of absolute cerebral blood flow (CBF), either by graphical Patlak-Gjedde analysis (PGA) or by spectral analysis, (SA). Other methods estimate CBF by means of single-point arterial or venous sampling. The aim of this study was to evaluate radionuclide scanning and single-point venous sampling as. potential clinical non- to minimally invasive methods for CBF determination in a large set of carefully screened healthy volunteers over the adult age range. Eighty-three carefully screened healthy volunteers (20-81 years, 43 males, 40 females) underwent planar radionuclide angiography with 925 MBq Tc-99m-ECD. After correction for camera dead-time loss, hemispheric CBF was calculated from brain perfusion indices (BPI): BPIG for PGA and BPIS for SA. Of the volunteers, 49 also underwent venous sampling 6 min post injection, from which the lipophilic octanol. extraction fraction and hemispheric brain fractionation index (BFI) were determined. All datasets were correlated and evaluated as a function of age and gender. Intrasubject variability for the BPI measurements was assessed in 11 volunteers by repeat study within 2 weeks of the first acquisition. Graphical and spectral analysis BPIs were strongly correlated (R=0.846, P <0.00001). This correlation coefficient increased to R=0.903 for the 74 Cases in which graphical analysis was not hampered by temporal tracer retention in cervicobrachial venous valves. The BFI was weakly correlated to both BPI indices (BPIG: R=0.34, P=0.02; BPIS: R=0.31, P=0.04). The right hemisphere showed significant asymmetry for BPIs (AI=2.7%+/-4.3%, P <0.001), in correspondence with previous Tc-99m-ECD data. BPIG, BPIs and BFI were all inversely related to age, with an increased gradient after the age of 55 years, while there was no significant gender difference. The ratio of BPIG to BIPS, which is a measure of the cerebral extraction fraction for Tc-99m-ECD, was not dependent on age. Intersubject variability was 15.5% for both radionuclide scanning-based methods and 18.2% for venous sampling, and in all cases was independent of age. A much lower intrasubject variability was observed for BPIS (7.2%) than for BPIG (12.6%). This study provides reference values for normal perfusion indices assessed by graphical and spectral analysis. The results also indicate that spectral analysis allows the most reproducible estimate of hemispheric perfusion by means of an operator-independent and objective approach. Whereas accurate calibration of normal BPIs values to hemispheric CBF with established methods needs to be performed, non-invasive calculation of regional absolute CBF using Tc-99m-ECD is possible by application of a linearisation algorithm

Estimation of crystal timing properties and efficiencies for the improvement of (joint) maximum-likelihood reconstructions in TOF-PET

With increasing improvements in the time of flight (TOF) resolution of positron emission tomography (PET) scanners, an accurate model of the TOF measurements is becoming increasingly important. This work considers two parameters of the TOF kernel; the relative positioning of the timing data-bins and the timing resolution along each line of response (LOR). Similar to an existing data-driven method, we assume that any shifts of data-bins along lines of response can be modelled as differences between crystal timing offsets. Inspired by this, timing resolutions of all LORs are modelled as the hypotenuse of timing resolutions of the crystal-pairs in coincidence. Furthermore, in order to mitigate the influence of potential inaccuracies of detector-pair sensitivities on crystal timing resolutions, relative LOR sensitivities are modelled as the product of efficiency factors for the two crystals in coincidence. We validate estimating maps of crystal timing offsets, timing resolutions and efficiencies from the emission data using noisy simulations of a brain phantom. Results are shown for phantom and patient data scanned on clinically available TOF-PET scanners. We find that the estimation of crystal timing resolutions is more sensitive to the data statistics than the estimation of crystal timing offsets. As a result, estimation of crystal timing properties could either be limited to high count emission data, or be obtained utilizing additional regularizations on the estimates. Using a more accurate model of the TOF acquisition, improvements are observed in standard activity reconstructions as well as joint reconstructions of activity and attenuation.status: Published onlin

Study of the relative heat-defect and correction factors of a water calo-rimetric determination of absorbed dose to water in high energy photon beams.

C